METHODS, TREATMENT, AND COMPOSITIONS FOR CHARACTERIZING THYROID NODULE

Abstract

The current disclosure provides, inter alia, method of determining benign nodules from thyroid cancer in a subject that is found to have a thyroid nodule, method of treating thyroid cancer in a subject detected to have thyroid cancer by the method of the current disclosure, compositions for determining benign nodules from thyroid cancer in a subject, and kits including reagents and composition for determining benign nodules from thyroid cancer in a subject.

Description

RELATED APPLICATION

[0001] This application claims the benefit of priority under 35 U.S.C. .sctn.119(e) to U.S. Provisional Application No. 62/196,678, filed Jul. 24, 2015, the content of which is incorporated herein by reference in its entirety.

INCORPORATION-BY-REFERENCE OF SEQUENCE LISTING

[0002] The content of the text file named "48440-573001 US_ST25.TXT", which was created on Jul. 22, 2016, and is 328.827 bytes in size, is hereby incorporated by reference in its entirety.

BACKGROUND OF THE DISCLOSURE

[0003] Palpable thyroid nodules are typically detected in 2-6% of the population, and this increases to 19-35% with ultrasound detection (Dean D S and Gharib H. Best Pract Res Clin Endocrinol Metab 2008; 22:901-11). Approximately 5-15% of thyroid nodules are found to be thyroid cancer, making the existence of a nodule clinically relevant. Fine needle aspiration (FNA) with cytology is currently the standard diagnostic procedure used to evaluate thyroid nodules. However, in as many as 30% of cases, the cytological diagnosis is indeterminate because of cytological features that overlap between benign and malignant nodules. For most indeterminate cases half or the entire thyroid is resected, yet as many as 80% of these cases are found to be benign.

[0004] Most thyroid nodules do not cause symptoms. Often, thyroid nodules are discovered incidentally during a routine physical examination or on imaging tests like CT scans or neck ultrasound done for completely unrelated reasons. Occasionally, patients themselves find thyroid nodules by noticing a lump in their neck while looking in a mirror, buttoning their collar, or fastening a necklace. Abnormal thyroid function tests may occasionally be the reason a thyroid nodule is found. Thyroid nodules may produce excess amounts of thyroid hormone causing hyperthyroidism. However, most thyroid nodules, including those that cancerous, are actually non-functioning, meaning current diagnostic test readouts such as the level of Thyroid-Stimulating Hormone (TSH) are normal. Rarely, patients with thyroid nodules may complain of pain in the neck, jaw, or ear. If a nodule is large enough to compress the windpipe or esophagus, it may cause difficulty with breathing, swallowing, or cause a "tickle in the throat". Even less commonly, hoarseness can be caused if the nodule invades the nerve that controls the vocal cords but this is usually related to thyroid cancer.

[0005] Molecular testing is a potential alternative to cytopathological examination. However, FNA molecular testing based on DNA mutations frequently fails. There are two major reasons for this failure: (i) not all papillary thyroid carcinoma (PTC) specimens are characterized by a common set of cancer associated mutations, and (ii) cancer associated mutations like KRAS are frequently found in benign thyroid nodule (BTN) specimens. At the same time commercial diagnostic tests for FNA based on transcriptional activity and currently implemented in clinical practice is complicated due to RNA instability and associated with only an approximately 50% positive predictive value. Thus, there is an urgent need for highly sensitive, low cost biomarker panels that can accurately diagnose thyroid nodules from FNA biopsies.

BRIEF SUMMARY OF THE DISCLOSURE

[0006] The present subject matter provides, inter alia, a method of determining benign nodules from thyroid cancer in a subject that is found to have a thyroid nodule, a method of treating thyroid cancer in a subject detected to have thyroid cancer, compositions for determining benign nodules from thyroid cancer in a subject, and kits including reagents and compositions for determining benign nodules from thyroid cancer in a subject.

[0007] In embodiments, aspects of the present subject matter provide a method of detecting methylation or unmethylation of a thyroid nodule DNA of a subject, the method including: (i) isolating DNA from a thyroid nodule of the subject thereby forming isolated thyroid nodule DNA, (ii) contacting the isolated thyroid nodule DNA with a bisulfite salt (such as sodium bisulfite) thereby forming a reacted thyroid nodule DNA, (iii) detecting the presence or absence of uracil in the reacted thyroid nodule DNA at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of the thyroid nodule DNA of the subject.

[0008] Also provided is a method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof. The method includes isolating DNA from a thyroid nodule of the subject thereby forming isolated thyroid nodule DNA. The isolated thyroid nodule DNA is contacted with sodium bisulfite thereby forming a reacted thyroid nodule DNA. The presence or absence of uracil is detected in the reacted thyroid nodule DNA at a methylation site set forth in Table 1 thereby determining thyroid cancer in the subject.

[0009] In embodiments, provided herein is a method of treating thyroid cancer in a subject by administering to the subject an active agent for treating thyroid cancer. The method includes identifying the subject for treatment by a method including isolating DNA from a thyroid nodule of the subject thereby forming isolated thyroid nodule DNA. The isolated thyroid nodule DNA is contacted with sodium bisulfite thereby forming a reacted thyroid nodule DNA. The presence or absence of uracil in the reacted thyroid nodule DNA is detected at a methylation site set forth in Table 1 thereby determining thyroid cancer in the subject.

[0010] Also included herein is a deoxyribonucleic acid 5 to 100, 5 to 200, 5 to 300, or at least about 5, 50, 100, 150, 200, 250, 300, or more nucleotides in length including a uracil-containing sequence identical to at least a 5 contiguous nucleotides within a sequence including SEQ ID NO: 1 to SEQ ID NO:550.

[0011] In embodiments, provided herein is an oligonucleotide 5 to 100, 5 to 200, 5 to 300, or at least about 5, 50, 100, 150, 200, 250, 300, or more nucleotides in length including identical or complementary to at least 5, 10, 20, 25, 50, 100, 150, 200, 250, or 300 contiguous nucleotides within a sequence including SEQ ID NO: 1 to SEQ ID NO:550.

[0012] Aspects of the present subject matter also include a deoxyribonucleic acid including SEQ ID NO: 551 to SEQ ID NO: 782, in which the nucleic acid is hybridized to a complementary DNA sequence having uridine or cytosine.

[0013] Also provided is a kit including a plurality (e.g., at least about 10, 20, 40, 50, 100, 150, 200, 225, or 232) nucleic acids each independently comprising SEQ ID NO: 551 to SEQ ID NO: 782, in which the nucleic acids do not simultaneously include the same sequence of SEQ ID NO: 551 to SEQ ID NO: 782.

[0014] Aspects of the present subject matter also provide a system for detecting methylation or unmethylation of a thyroid nodule deoxyribonucleic acid (DNA) of a subject. The system can include at least one processor; and at least one memory including program code which when executed by the at least one memory provides operations. The operations can include: isolating DNA from a thyroid nodule of the subject thereby forming isolated thyroid nodule DNA; contacting the isolated thyroid nodule DNA with bisulfite salt thereby forming a reacted thyroid nodule DNA; detecting a presence or absence of uracil in the reacted thyroid nodule DNA at a plurality of methylation sites set forth in Table 1, thereby detecting methylation or unmethylation of the thyroid nodule DNA of the subject; and generating a diagnosis for the subject based at least in part on the presence or absence of uracil in the reacted thyroid nodule DNA at the plurality of methylation sites set forth in Table 1; and providing, via a user interface, the diagnosis for the subject.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] FIGS. 1A-1B show a drawing defining a threshold for thyroid adenoma specific signature for individual cytosine regions. FIG. 1A: Adenoma specific hypomethylation signature. FIG. 1B: Adenoma specific hypermethylation signature.

[0016] FIGS. 2A and 2B show 364 cytosines associated with BTN or PTC specific DNA methylation changes. Legend (FIG. 2A): Cancer specific signature (gray); benign specific signature (black). FIG. 2B: 364 CpG sites associated with benign- and thyroid cancer-specific DNA methylation changes. Each row represents a single cytosine. Each column represents tissue specimen. Dark gray, light gray and black indicate high, low and medium levels of DNA methylation, respectively. Abbreviation "A" is for thyroid benign nodule and "T" is for thyroid cancer.

[0017] FIGS. 3A-3C depict exemplary thyroid cancer diagnostics based on DNA methylation signatures. FIG. 3A: Thyroid cancer diganostics based on benign DNA methylation signature, cancer DNA methylation signature and cancer risk scores. FIG. 3B: DNA methylation signatures for malignant and benign thyroid nodules according to leave one-out-cross-validation technique. Specimens with indeterminate epigenetic signature are underlined. Abbreviation "A" is for thyroid benign nodule and "T" is for thyroid cancer. FIG. 3C: Algorithm for the diagnosis prediction based on BTN. PTC and cancer risk scores.

[0018] FIG. 4 depicts a block diagram illustrating an exemplary thyroid cancer diagnostics system.

[0019] FIG. 5 depicts a flowchart illustrating an exemplary process for diagnosing thyroid cancer.

[0020] FIG. 6 depicts a flowchart illustrating an exemplary process for diagnosing thyroid cancer.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0021] Provided herein are, inter alia, compositions, methods, kits, and systems for detecting unmethylated DNA. In embodiments, compositions, methods, kits, and systems for detecting unmethylated DNA from thyroid nodule are included herein.

[0022] The following definitions are included for the purpose of understanding the present subject matter and for constructing the appended patent claims. Abbreviations used herein have their conventional meaning within the chemical and biological arts.

DEFINITIONS

[0023] The term "thyroid nodule" is used according to its plain ordinary meaning and refers to an abnormal growth of thyroid cells. The abnormal growth may form, for example, a mass or lump within or on the thyroid gland. The mass or lump may be fluid-filled or solid. The thyroid nodules may be benign (noncancerous) or cancerous.

[0024] Thyroid fine needle aspiration biopsy (FNA or FNAB): For a fine needle biopsy, a needle is used to withdraw cells from a thyroid nodule. In embodiments, several samples are taken from different parts of the nodule, e.g., to increase the chance of finding cancerous cells if they are present. In embodiments, a sample is taken from one part of the nodule. In embodiments, examination of the cells under a microscope is not necessary. In non-limiting examples, the needle used for FNA is a 20-35 gauge needle (such as a 23, 24 or 25 gauge needle).

[0025] The term "disease" refers to any deviation from the normal health of a mammal and includes a state when disease symptoms are present, as well as conditions in which a deviation (e.g., infection, gene mutation, genetic defect, etc.) has occurred, but symptoms are not yet manifested. According to the present disclosure, the methods disclosed herein are suitable for use in a patient that is a member of the Vertebrate class. Mammalia, including, without limitation, primates, livestock and domestic pets (e.g., a companion animal). Typically, a patient will be a human patient. As used herein, a "symptom" of a disease includes and clinical or laboratory manifestation associated with the disease, and is not limited to what a subject can feel or observe.

[0026] The terms "subject," "patient," "individual," and the like as used herein are not intended to be limiting and can be generally interchanged. That is, an individual described as a "patient" does not necessarily have a given disease, but may be merely seeking medical advice.

[0027] The term "subject" as used herein includes all members of the animal kingdom that may suffer from the indicated disorder. In some aspects, the subject is a mammal, and in some aspects, the subject is a human.

[0028] It must be noted that as used herein and in the appended embodiments, the singular forms "a," "an," and "the" include the plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "a disease," "a disease state", "a nucleic acid" or "a CpG site" is a reference to one or more such embodiments, and includes equivalents thereof known to those skilled in the art and so forth.

[0029] Throughout the description and claims of this specification the word "comprise" and other forms of the word, such as "comprising" and "comprises." means including but not limited to, and is not intended to exclude, for example, other components.

[0030] A "control" sample or value refers to a sample that serves as a reference, usually a known reference, for comparison to a test sample. For example, a test sample can be taken from a patient suspected or at risk of having thyroid cancer and compared to samples from a known thyroid cancer patient, or a known normal (non-disease) individual. A control can also represent an average value gathered from a population of similar individuals, e.g., thyroid cancer patients or healthy individuals with a similar medical background, same age, weight, etc. A control value can also be obtained from the same individual, e.g., from an earlier-obtained sample, prior to disease, or prior to treatment. One of skill will recognize that controls can be designed for assessment of any number of parameters.

[0031] One of skill in the art will understand which controls are valuable in a given situation and be able to analyze data based on comparisons to control values. Controls are also valuable for determining the significance of data. For example, if values for a given parameter are widely variant in controls, variation in test samples will not be considered as significant.

[0032] The term "diagnosis" refers to a relative probability that a disease is present in the subject. Similarly, the term "prognosis" refers to a relative probability that a certain future outcome may occur in the subject. For example, in the context of the present disclosure, prognosis can refer to the likelihood that an individual will develop a disease, or the likely severity of the disease (e.g., severity of symptoms, rate of functional decline, survival, etc.). The terms are not intended to be absolute, as will be appreciated by any one of skill in the field of medical diagnostics.

[0033] "Nucleic acid" or "oligonucleotide" or "polynucleotide" or grammatical equivalents used herein means at least two nucleotides covalently linked together. Oligonucleotides are typically from about 5, 6, 7, 8, 9, 10, 12, 15, 25, 30, 40, 50 or more nucleotides in length, up to about 100 nucleotides in length. Nucleic acids, including ribonucleic acids (RNA) and deoxyribonucleic acids (DNA), and polynucleotides are a polymers of any length, including longer lengths. e.g., 200, 300, 500, 1000, 2000, 3000, 5000, 7000, 10,000, etc. A nucleic acid of the present invention will generally contain phosphodiester bonds, although in some cases, nucleic acid analogs are included that may have alternate backbones, comprising, e.g., phosphoramidate, phosphorothioate, phosphorodithioate, or O-methylphophoroamidite linkages (see Eckstein, Oligonucleotides and Analogues: A Practical Approach, Oxford University Press); and peptide nucleic acid backbones and linkages. Other analog nucleic acids include those with positive backbones; non-ionic backbones, and non-ribose backbones, including those described in U.S. Pat. Nos. 5,235,033 and 5,034,506, and Chapters 6 and 7, ASC Symposium Series 580. Carbohydrate Modifications in Antisense Research, Sanghui & Cook, eds. Nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids. Modifications of the ribose-phosphate backbone may be done for a variety of reasons, e.g., to increase the stability and half-life of such molecules in physiological environments or as probes on a biochip. Mixtures of naturally occurring nucleic acids and analogs can be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made.

[0034] The term "bp" and the like refer, in the usual and customary sense, to the indicated number of base pairs.

[0035] The terms "identical" or percent "identity," in the context of two or more nucleic acids (e.g., genomic sequences or subsequences or coding sequences) or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more identity over a specified region), when compared and aligned for maximum correspondence over a comparison window, or designated region as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Such sequences are then said to be "substantially identical." This definition also refers to the compliment of a test sequence. Optionally, the identity exists over a region that is at least about 10 to about 100, about 20 to about 75, about 30 to about 50 amino acids or nucleotides in length.

[0036] An example of algorithms suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., Nuc. Acids Res. 25:3389-3402 (1977) and Altschul et al., J. Mol. Biol. 215:403-410 (1990), respectively. As will be appreciated by one of skill in the art, the software for performing BLAST analyses is publicly available through the website of the National Center for Biotechnology Information.

[0037] A "label" or a "detectable moiety" is a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical, or other physical means. For example, useful labels include .sup.32P, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin, digoxigenin, or haptens and proteins or other entities which can be made detectable, e.g., by incorporating a radiolabel into a peptide or antibody specifically reactive with a target peptide. Any method known in the art for conjugating an antibody to the label may be employed, e.g., using methods described in Hermanson, Bioconjugate Techniques 1996, Academic Press, Inc., San Diego.

[0038] The term "associated" or "associated with" in the context of a substance (e.g., level of uracil or methylation level in a thyroid nodule) does not necessarily mean that the disease is caused by (in whole or in part), or a symptom of the disease is caused by (in whole or in part) the substance or substance activity or function (i.e., level of uracil in the regions of chromosomes assayed).

[0039] The term "unmethylated DNA" or "demethylated DNA" means DNA that lacks a methyl group conjugated to cytosine in a segment of the DNA. DNA methylation typically occurs in a CpG dinucleotide context. DNA methylation at the 5' position of cytosine may have the specific effect on gene expression in vivo. DNA methylation may also form the basis of epigenetic structure, which typically enables a single cell to grow into multiple organs or perform multiple functions.

[0040] The CpG sites or CG sites are regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases along its length. "CpG" is shorthand for "-C-phosphate-G-", that is, cytosine and guanine separated by only one phosphate; phosphate links any two nucleosides together in DNA. The "CpG" notation is used to distinguish this linear sequence from the CG base-pairing of cytosine and guanine. The CpG notation can also be interpreted as the cytosine being 5' prime to the guanine base.

[0041] In embodiments, methylation is detected based on a chemical reaction of sodium bisulfite with DNA that converts unmethylated cytosines of CpG dinucleotides to uracil or UpG. However, methylated cytosine is not converted in this process, the methods described herein allow determination of methylation status as methylated or unmethylated.

Evaluation of Thyroid Fine Needle Biopsies by Visual Examination

[0042] Cells in a thyroid vine needle biopsy sample may be examined under a microscope by, e.g., a pathologist. The report of a thyroid fine needle biopsy followed by examination under a microscope will usually indicate one of the following findings:

[0043] 1. The nodule is benign (noncancerous). This result is obtained in up to 80% of biopsies. The risk of overlooking a cancer when the biopsy is benign is generally less than 3 in 100 tests or 3%. This is even lower when the biopsy is reviewed by an experienced pathologist at a major medical center. Generally, benign thyroid nodules do not need to be removed unless they are causing symptoms like choking or difficulty swallowing. Follow up ultrasound exams are important. Occasionally, another biopsy may be required in the future, especially if the nodule grows over time.

[0044] 2. The nodule is malignant (cancerous) or suspicious for malignancy. A malignant result is obtained in about 5% of biopsies and is most often due to papillary cancer, which is the most common type of thyroid cancer. A malignant diagnosis has a >99% risk of cancer in the nodule. A suspicious biopsy has a 50-75% risk of cancer in the nodule. These diagnoses require surgical removal of the thyroid after consultation with the endocrinologist and surgeon.

[0045] 3. The nodule is indeterminate. This is actually a group of several diagnoses that may occur in up to 30% of cases. An indeterminate finding means that even though an adequate number of cells was removed during the fine needle biopsy, examination with a microscope cannot reliably classify the result as benign or cancer. The biopsy may be indeterminate because the nodule is described as a Follicular Lesion. These nodules are cancerous 20-30% of the time. However, under the current state of the art, the diagnosis can only be made by surgery. Because the odds that the nodule is not a cancer are much better by surgery (70-80%), only the side of the thyroid with the nodule is usually removed. If a cancer is found, the remaining thyroid gland is usually removed as well. If the surgery confirms that no cancer is present, no additional surgery to "complete" the thyroidectomy is necessary.

[0046] The biopsy may also be indeterminate because the cells from the nodule have features that cannot be placed in one of the other diagnostic categories. This diagnosis is called atypia, or a follicular lesion of undetermined significance. Diagnoses in this category will contain cancer rarely, so repeat evaluation with FNA or surgical biopsy to remove half of the thyroid containing the nodule is usually recommended.

[0047] 4. The biopsy may also be non-diagnostic or inadequate. This result indicates that not enough cells were obtained to make a diagnosis but is a common result if the nodule is a cyst. These nodules may require reevaluation with second fine needle biopsy, or may need to be removed surgically depending on the clinical judgment of the doctor.

[0048] Methods, compositions, kits, and systems provided herein provide significant advantages over the visual examination of biopsies.

Method of Detection Methylation Status of a Thyroid Nodule DNA

[0049] In an aspect, provided herein is a method of detecting methylation or unmethylation of a thyroid nodule DNA of a subject. The method includes: (i) isolating a thyroid nodule DNA molecule from a thyroid nodule of the subject thereby forming an isolated thyroid nodule DNA molecule, (ii) contacting the isolated thyroid nodule DNA molecule with a bisulfite salt (such as sodium bisulfite) thereby forming a reacted thyroid nodule DNA molecule, (iii) detecting the presence or absence of uracil in the reacted thyroid nodule DNA molecule at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of the thyroid nodule DNA molecule of the subject. In embodiments, contacting the isolated thyroid nodule DNA with a bisulfite salt comprises adding a solution comprising the bisulfite salt to a solution comprising the isolated single stranded DNA.

[0050] In an aspect, provided herein is a method of detecting methylation or unmethylation of a thyroid nodule DNA molecule of a subject comprising (i) isolating a plurality of thyroid nodule DNA molecules from the thyroid nodule of the subject thereby forming a plurality of isolated thyroid nodule DNA molecules, (ii) contacting the plurality of isolated thyroid nodule DNA molecules with the bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, (iii) detecting the level of reacted thyroid nodule DNA molecules in the plurality of reacted thyroid nodule DNA molecules having a uracil at a methylation site set forth in Table 1, thereby detecting the level of methylation or unmethylation in the plurality of thyroid nodule DNA molecules of the subject.

[0051] In an aspect, provided herein is a method of detecting methylation or unmethylation of a thyroid nodule DNA molecule of a subject comprising (i) isolating a plurality of thyroid nodule DNA molecules from the thyroid nodule of the subject thereby forming a plurality of isolated thyroid nodule DNA molecules, (ii) contacting the plurality of isolated thyroid nodule DNA molecules with the bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, (iii) detecting the presence or absence of uracil in a reacted thyroid nodule DNA molecule at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of the thyroid nodule DNA molecule of the subject.

[0052] In an aspect, provided herein is a method of detecting methylation or unmethylation of a thyroid nodule DNA of a subject. The method includes: (i) isolating a thyroid nodule DNA molecule from a thyroid nodule of the subject thereby forming an isolated thyroid nodule DNA molecule, (ii) contacting the isolated thyroid nodule DNA molecule with a bisulfite salt (such as sodium bisulfite) thereby forming a reacted thyroid nodule DNA molecule, (iii) amplifying the reacted thyroid nodule DNA molecule thereby forming a reacted thyroid nodule DNA amplicon molecule, (iv) detecting the presence or absence of thymidine in a reacted thyroid nodule DNA amplicon molecule at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of the thyroid nodule DNA molecule of the subject. In embodiments, contacting the isolated thyroid nodule DNA with a bisulfite salt comprises adding a solution comprising the bisulfite salt to a solution comprising the isolated single stranded DNA.

[0053] In an aspect, provided herein is a method of detecting methylation or unmethylation of a thyroid nodule DNA molecule of a subject comprising (i) isolating a plurality of thyroid nodule DNA molecules from the thyroid nodule of the subject thereby forming a plurality of isolated thyroid nodule DNA molecules, (ii) contacting the plurality of isolated thyroid nodule DNA molecules with the bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, (iii) amplifying the plurality of reacted thyroid nodule DNA molecules thereby forming a plurality of reacted thyroid nodule DNA amplicon molecules, (iv) detecting one or more thyroid nodule DNA amplicon molecules within the plurality of reacted thyroid nodule DNA amplicon molecules having a thymidine at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of the thyroid nodule DNA molecule of the subject.

[0054] In embodiments, detecting one or more thyroid nodule DNA amplicon molecules comprises detecting the level of one or more one or more thyroid nodule DNA amplicon molecules. In embodiments, detecting one or more thyroid nodule DNA amplicon molecules comprises detecting the level of reacted thyroid nodule DNA amplicon molecules in the plurality of reacted thyroid nodule DNA amplicon molecules having a thymidine at a methylation site set forth in Table 1, thereby detecting the level of methylation or unmethylation in the plurality of thyroid nodule DNA molecules of the subject.

[0055] In embodiments, detecting a level includes determining the number (e.g. quantitating) or molecules having, e.g., a thymidine or a uracil. In embodiments, detecting a level includes detecting the portion or proportion of a population or plurality of molecules having, e.g., a thymidine or a uracil.

[0056] In embodiments, the isolated thyroid nodule DNA sample is treated with a bisulfite reagent, e.g., a bisulfite salt (i.e., a process called DNA bisulfite conversion). Non-limiting examples of bisulfite salts include sodium bisulfite, potassium bisulfite, ammonium bisulfite, magnesium bisulfite, sodium metabisulfite, potassium metabisulfite, ammonium metabisulfite and magnesium metabisulfite. Bisulfite salts such as sodium bisulfite or ammonium bisulfite can convert cytosine to uracil and leave 5-methylcytosine (5-mC) the same. Thus after bisulfite treatment methylated cytosine in the DNA remains the same and unmodified cytosines will be changed to uracil. The bisulfite treatment can be performed by using the methods disclosed herein or in the art, and/or with commercial kits such as the Bisulflash DNA Modification Kit (Epigentek) and Imprint DNA Modification Kit (Sigma). For achieving the optimal bisulfite conversion, the bisulfite reaction should be carried out in an appropriate concentration of bisulfite reagents, appropriate temperature and appropriate reaction time period. A reagent such as potassium chloride that reduces thermophilic DNA degradation could also be used in bisulfite treatment so that the DNA bisulfite process can be much shorter without interrupting a completed conversion of unmethylated cytosine to uracil and without a significant thermodegradation of DNA resulted from depurination. In embodiments, a commercially available bisulfite treatment kit is used. A non-limiting example of such a kit is EZ DNA Methylation-Gold.TM. Kit (Zymo Research. Irvine, Calif., USA).

[0057] In embodiments, once DNA bisulfite conversion is complete, DNA is captured, desulphonated and washed. In embodiments, the bisulfite-treated DNA can be captured by, e.g., a solid matrix selected from silica salt, silica dioxide, silica polymers, magnetic beads, glass fiber, celite diatoms and nitrocellulose in the presence of high concentrations of chaotropic or non-chaotropic salts. In embodiments, the bisulfite-treated DNA is further desulphonated with an alkalized solution, preferably sodium hydroxide at concentrations from 10 mM to 300 mM. In embodiments, the DNA is then eluted and collected into a capped microcentrifuge tube. Non-limiting examples of elution solutions include DEPC-treated water and TE buffer (10 mM Tris-HCL, pH 8.0, and 1 mM EDTA).

[0058] In embodiments, the reacted thyroid nodule DNA resulting from bisulfite treatment is amplified. In embodiments, detecting the presence or absence of uracil in reacted thyroid nodule DNA molecule at a methylation site comprises amplifying the reacted thyroid nodule DNA molecule thereby forming a reacted thyroid nodule DNA amplicon molecule, and detecting the presence or absence of thymidine in a reacted thyroid nodule DNA amplicon molecule at the methylation site. In embodiments, a polymerase chain reaction (PCR) method is used for amplifying the reacted thyroid nodule DNA. PCR methods are known to those of ordinary skill in the art. In general, the PCR reactions can be set up by adding sample, dNTPs, and appropriate polymerase such as Taq polymerase, primers, and a buffer.

[0059] In embodiments, the method of detecting methylation or unmethylation of a thyroid nodule DNA of a subject, includes detecting methylation or unmethylation at a plurality of methylation sites set forth in Table 1. In embodiments, the plurality of methylation sites comprises at least about 2, 3, 4, 5, 10, 25, 50, 75, 80, 85, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, or 550, or 5-550 methylation sites. In embodiments, the plurality of methylation sites comprises less than about 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, 90, 85, 80, 75, 50, 25, or 10 methylation sites. In embodiments, the plurality of methylation sites is about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 50.75, 80, 85.90, 100, 150, 200.250, 300.350, 400, 450, 500, or 550, or 5-550 methylation sites. In embodiments, the plurality of methylation sites includes two or more methylation sites set forth in Table 1 and no other methylation sites.

[0060] In embodiments, the method includes detecting methylation or unmethylation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 200, 300, 400, or 500 of the following sites: Chromosome 1 (Chr1) position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chromosome 2 (Chr2) position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chromosome 3 (Chr3) position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chromosome 4 (Chr4) position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chromosome 5 (Chr5) position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chromosome 6 (Chr6) position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chromosome 7 (Chr7) position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chromosome 8 (Chr8) position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chromosome 9 (Chr9) position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chromosome 10 (Chr10) position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chromosome 11 (Chr11) position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chromosome 12 (Chr12) position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chromosome 13 (Chr13) position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chromosome 14 (Chr14) position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chromosome 15 (Chr15) position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chromosome 16 (Chr16) position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chromosome 17 (Chr17) position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chromosome 18 (Chr18) position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chromosome 19 (Chr19) position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chromosome 20 (Chr20) position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chromosome 22 (Chr22) position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0061] In embodiments, the method includes detecting methylation or unmethylation of at least 1 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0062] In embodiments, the method includes detecting methylation or unmethylation of at least 2 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0063] In embodiments, the method includes detecting methylation or unmethylation of at least 3 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0064] In embodiments, the method includes detecting methylation or unmethylation of at least 4 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0065] In embodiments, the method includes detecting methylation or unmethylation of at least 5 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0066] In embodiments, the method includes detecting methylation or unmethylation of at least 6 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0067] In embodiments, the method includes detecting methylation or unmethylation of at least 7 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0068] In embodiments, the method includes detecting methylation or unmethylation of at least 8 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0069] In embodiments, the method includes detecting methylation or unmethylation of at least 9 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0070] In embodiments, the method includes detecting methylation or unmethylation of at least 10 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0071] In embodiments, the method includes detecting methylation or unmethylation of at least 50 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0072] In embodiments, the method includes detecting methylation or unmethylation of at least 100 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0073] In embodiments, the method includes detecting methylation or unmethylation of at least 200 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0074] In embodiments, the method includes detecting methylation or unmethylation of at least 300 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0075] In embodiments, the method includes detecting methylation or unmethylation of at least 400 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0076] In embodiments, the method includes detecting methylation or unmethylation of at least 500 of the following sites: Chr1 position 2996653, Chr1 position 11979164, Chr1 position 12655938, Chr1 position 16450525, Chr1 position 16450542, Chr1 position 16450545, Chr1 position 16469987, Chr1 position 17494491, Chr1 position 25473203, Chr1 position 27640460, Chr1 position 29565080, Chr1 position 38493013, Chr1 position 38493030, Chr1 position 38493074, Chr1 position 46713777, Chr1 position 46914121, Chr1 position 46955744, Chr1 position 55008344, Chr1 position 109816092, Chr1 position 109816111, Chr1 position 110074669, Chr1 position 110074681, Chr1 position 110074685, Chr1 position 150949856, Chr1 position 150949857, Chr1 position 153540282, Chr1 position 155162704, Chr1 position 155162714, Chr1 position 156676611, Chr1 position 157611881, Chr1 position 182205324, Chr1 position 204118999, Chr1 position 206741875, Chr1 position 206741989, Chr1 position 212587673, Chr1 position 212841198, Chr1 position 223403952, Chr1 position 233430972, Chr1 position 234342767, Chr2 position 3454277, Chr2 position 8793724, Chr2 position 20412441, Chr2 position 42329402, Chr2 position 42329494, Chr2 position 55289272, Chr2 position 65064865, Chr2 position 70823641, Chr2 position 73143689, Chr2 position 74454110, Chr2 position 122014529, Chr2 position 128158884, Chr2 position 128158910, Chr2 position 203114171, Chr2 position 218221671, Chr2 position 219745335, Chr2 position 238341465, Chr2 position 238341542, Chr2 position 238341546, Chr2 position 238774763, Chr3 position 13323642, Chr3 position 14180153, Chr3 position 45209073, Chr3 position 45209207, Chr3 position 52525100, Chr3 position 62589658, Chr3 position 65388317, Chr3 position 65388388, Chr3 position 73599302, Chr3 position 195636893, Chr3 position 197093846, Chr4 position 3743223, Chr4 position 5755716, Chr4 position 5755717, Chr4 position 5755728, Chr4 position 5755729, Chr4 position 5755734, Chr4 position 8372861, Chr4 position 57548289, Chr5 position 1118280, Chr5 position 34564389, Chr5 position 73871907, Chr5 position 78013596, Chr5 position 78013643, Chr5 position 137802650, Chr5 position 139051189, Chr5 position 167838221, Chr5 position 177541401, Chr5 position 180018672, Chr5 position 180101026, Chr6 position 3394325, Chr6 position 3887581, Chr6 position 7236568, Chr6 position 7728692, Chr6 position 34203617, Chr6 position 37751320, Chr6 position 41410682, Chr6 position 41438516, Chr6 position 41438575, Chr6 position 43464150, Chr6 position 158734279, Chr7 position 989235, Chr7 position 2673543, Chr7 position 73508602, Chr7 position 105079565, Chr7 position 105079631, Chr7 position 151425103, Chr7 position 151425104, Chr8 position 11764017, Chr8 position 21647308, Chr8 position 22548399, Chr8 position 22548483, Chr8 position 133570537, Chr8 position 141320393, Chr8 position 141320410, Chr9 position 6566568, Chr9 position 16197862, Chr9 position 34591313, Chr9 position 98225096, Chr9 position 126126741, Chr9 position 132083428, Chr9 position 136077410, Chr9 position 139655018, Chr9 position 140205985, Chr9 position 140205985, Chr9 position 140205997, Chr10 position 3929071, Chr10 position 30047012, Chr10 position 79702989, Chr10 position 87984905, Chr10 position 94838789, Chr10 position 102131187, Chr10 position 104196489, Chr10 position 111766879, Chr10 position 112258886, Chr10 position 112258984, Chr10 position 112259015, Chr10 position 116391763, Chr10 position 120011530, Chr10 position 126172714, Chr10 position 126172747, Chr11 position 556355, Chr11 position 821282, Chr11 position 12188937, Chr11 position 12188948, Chr11 position 12188995, Chr11 position 36057726, Chr11 position 48070143, Chr11 position 48070163, Chr11 position 48070166, Chr11 position 48070174, Chr11 position 65158294, Chr11 position 65158342, Chr11 position 65297089, Chr11 position 66104481, Chr11 position 66104485, Chr11 position 66104578, Chr11 position 68608767, Chr11 position 70236292, Chr11 position 70236320, Chr11 position 70236331, Chr11 position 115530032, Chr11 position 117950310, Chr11 position 117950329, Chr11 position 117950361, Chr11 position 117950362, Chr11 position 119293593, Chr12 position 679803, Chr12 position 26039132, Chr12 position 31004558, Chr12 position 45610695, Chr12 position 45610701, Chr12 position 45610702, Chr12 position 45610706, Chr12 position 50286016, Chr12 position 52243258, Chr12 position 52243286, Chr12 position 54145732, Chr12 position 54145741, Chr12 position 54145825, Chr12 position 56115043, Chr12 position 66262229, Chr12 position 66262230, Chr12 position 66262233, Chr12 position 66262234, Chr12 position 77266621, Chr12 position 117580102, Chr12 position 123435962, Chr12 position 123436011, Chr12 position 123436065, Chr12 position 123540893, Chr13 position 20735797, Chr13 position 23500419, Chr13 position 46771519, Chr13 position 46771520, Chr13 position 53313426, Chr13 position 113807393, Chr14 position 38599118, Chr14 position 69170010, Chr14 position 75701632, Chr14 position 75701643, Chr14 position 90850454, Chr14 position 97524282, Chr14 position 103541602, Chr14 position 103768055, Chr14 position 104209000, Chr14 position 104209068, Chr14 position 104354645, Chr14 position 104360487, Chr15 position 41068807, Chr15 position 61152225, Chr15 position 61152253, Chr15 position 61152313, Chr15 position 65186440, Chr15 position 68851629, Chr15 position 70667596, Chr15 position 70767206, Chr15 position 75251486, Chr15 position 77984014, Chr15 position 77989064, Chr15 position 83952081, Chr15 position 85402496, Chr15 position 85402497, Chr15 position 99417337, Chr16 position 1231873, Chr16 position 1458639, Chr16 position 3023231, Chr16 position 23135832, Chr16 position 29616265, Chr16 position 31009547, Chr16 position 31009548, Chr16 position 31009590, Chr16 position 57793674, Chr16 position 57793715, Chr16 position 57793727, Chr16 position 70771056, Chr16 position 70771079, Chr16 position 70771141, Chr16 position 77332010, Chr16 position 78540378, Chr16 position 79333435, Chr16 position 84262419, Chr16 position 88701114, Chr16 position 89988308, Chr16 position 89988644, Chr17 position 1509928, Chr17 position 1509945, Chr17 position 1509952, Chr17 position 1509953, Chr17 position 7644013, Chr17 position 16323460, Chr17 position 16323473, Chr17 position 16924561, Chr17 position 16924562, Chr17 position 16924594, Chr17 position 17717918, Chr17 position 17718591, Chr17 position 18139506, Chr17 position 35278031, Chr17 position 39677570, Chr17 position 40826257, Chr17 position 43037426, Chr17 position 43200096, Chr17 position 43200239, Chr17 position 43510142, Chr17 position 47987828, Chr17 position 48178379, Chr17 position 48596391, Chr17 position 48764165, Chr17 position 55701962, Chr17 position 73584599, Chr17 position 73993165, Chr17 position 75827716, Chr17 position 76882243, Chr17 position 78765910, Chr17 position 79544478, Chr17 position 80696474, Chr18 position 19751759, Chr18 position 21440760, Chr18 position 45555437, Chr18 position 45555438, Chr18 position 46547891, Chr18 position 55888885, Chr18 position 56452096, Chr18 position 56452476, Chr18 position 56887181, Chr18 position 76002973, Chr18 position 77331090, Chr19 position 677895, Chr19 position 884044, Chr19 position 884059, Chr19 position 884105, Chr19 position 884115, Chr19 position 1136511, Chr19 position 1177605, Chr19 position 1177612, Chr19 position 1177640, Chr19 position 1860601, Chr19 position 1860607, Chr19 position 2503954, Chr19 position 3434917, Chr19 position 3434921, Chr19 position 3434930, Chr19 position 3434939, Chr19 position 3434952, Chr19 position 3434954, Chr19 position 3434962, Chr19 position 3434964, Chr19 position 3434979, Chr19 position 3434985, Chr19 position 4052713, Chr19 position 4052714, Chr19 position 4052749, Chr19 position 4374591, Chr19 position 5013982, Chr19 position 5048836, Chr19 position 5048867, Chr19 position 5048877, Chr19 position 8367279, Chr19 position 8428573, Chr19 position 10254577, Chr19 position 10254578, Chr19 position 10463956, Chr19 position 10464137, Chr19 position 13203671, Chr19 position 13266925, Chr19 position 13266934, Chr19 position 13266970, Chr19 position 13842142, Chr19 position 14248494, Chr19 position 15375465, Chr19 position 17218912, Chr19 position 17346702, Chr19 position 17346702, Chr19 position 18157161, Chr19 position 18157221, Chr19 position 18157258, Chr19 position 18415877, Chr19 position 18415890, Chr19 position 30606642, Chr19 position 35531842, Chr19 position 44303112, Chr19 position 47173037, Chr19 position 47316268, Chr19 position 47778278, Chr19 position 47778298, Chr20 position 34206950, Chr20 position 36771969, Chr20 position 48993661, Chr20 position 58406398, Chr20 position 61976049, Chr20 position 61976073, Chr20 position 62588571, Chr20 position 62588579, Chr22 position 19738127, Chr22 position 35965176, Chr22 position 36549809, Chr22 position 36973375, Chr22 position 37447953, Chr22 position 37914998, Chr22 position 38307317, Chr22 position 39662794, and Chr22 position 45622980.

[0077] In embodiments, a method provided herein is practiced for a subject more than once over time. In embodiments, methylation or unmethylation of thyroid nodule DNA from a subject is assessed using a method provided herein at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more times. In embodiments, the method is repeated at least once every 4, 6, 8, 12 or 18 months, or at least once every 2, 3, 4, or 5 more years.

[0078] In embodiments, the method includes: (i) isolating DNA from multiple cells of a thyroid nodule of the subject thereby forming a plurality of isolated thyroid nodule DNA molecules, (ii) contacting the plurality of isolated thyroid nodule DNA molecules with a bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, (iii) detecting the proportion of DNA molecules in the plurality of reacted thyroid nodule DNA molecules having a uracil at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of said thyroid nodule DNA of the subject.

[0079] The methylation of a CpG site of interest may vary between individual cells (and even between chromosome pairs of individual cells) in a biological sample. When DNA is obtained from a biological sample and treated with a bisulfite salt to convert unmethylated cytosines to uracils, the bisulfite-treated DNA will typically contain (i) a proportion of DNA molecules with a cytosine at the site of interest (indicating that the site was methylated); and (ii) a proportion of DNA molecules with a uracil at the site of interest (indicating that the site was unmethylated). Since a uracil at a site of interest in bisulfite-treated DNA indicates that the site was unmethylated in the untreated DNA, a thymidine at the corresponding site in an amplicon of the bisulfite-treated DNA (e.g., an amplicon obtained by PCR) also indicates that the site was unmethylated in the untreated DNA.

[0080] In embodiments, the level of methylation at a site of interest is the proportion of bisulfite-treated DNA molecules having a cytosine rather than a uracil at that site of interest. In embodiments, the level of methylation at a site of interest is the proportion of amplicons of bisulfite-treated DNA molecules having a cytosine rather than a thymidine at that site of interest.

[0081] In embodiments, the level of unmethylation at a site of interest is the proportion of bisulfite-treated DNA molecules having a uracil rather than a cytosine at that site of interest. In embodiments, the level of unmethylation at a site of interest is the proportion of amplicons of bisulfite-treated DNA molecules having a thymidine rather than a cytosine at that site of interest. In Table 1, an indicated level of uracil is the proportion of bisulfite-treated DNA molecules having a uracil rather than a cytosine at the specified methylation site. The same levels listed in Table 1 also apply to the thymidine levels at a site of interest in an amplicon, i.e., the proportion of amplicons (derived from the PCR amplification of bisulfite-treated DNA molecules) having a thymidine rather than a cytosine at the specified methylation site.

[0082] The level of DNA methylation at a site of interest (e.g., a methylation site listed in Table 1) may be determined using sequencing technology. Sequencing technology can reveal nucleotide sequence variations in a plurality of DNA molecules at a single nucleotide base resolution. For example, the proportions of corresponding DNA molecules having a uracil, a thymidine, and/or a cytosine at a site may be determined. A non-limiting example of a sequencing-based method for determining the methylation level at a site of interest is described in Masser et al. (2015) Targeted DNA Methylation Analysis by Next-generation Sequencing. J Vis Exp. (96): 52488, the entire content of which is incorporated herein by reference.

[0083] The chromosomal positions listed in Tables 1-4 relate to the human genome that is publically accessible in the University of California Santa Cruz (UCSC) genome browser database under accession number HG19, the entire content of which is incorporated herein by reference in its entirety. Non-limiting information regarding the UCSC Genome Browser is provided in Kent W J, Sugnet C W, Furey T S, Roskin K M, Pringle T H, Zahler A M, Haussler D. The human genome browser at UCSC. Genome Res. 2002 June; 12(6):996-1006, the entire content of which is incorporated herein by reference. Each methylation site of interest listed in Table 1 may be located in other human genomes (e.g., within the genome of a specific subject or group of subjects) by replacing every U and R in the corresponding sequence with a C and then searching for the location of the X within a reference genome by aligning the sequence against the reference genome. For example, the methylation site of interest "X" in SEQ ID NO: 1 may be located within a genome by replacing each U and R in SEQ ID NO: 1 with a C (to obtain the pre-bisulfite-modified sequence having an X at the site of interest) and then aligning the sequence against the genome using a BLAST algorithm. Also expressly provided, disclosed, and incorporated herein is the non-bisulfite-modified sequence corresponding to each of SEQ ID NOS: 1-550. The non-bisulfite-modified sequence corresponding to each of SEQ ID NOS:1-550 is each respective sequence in which each U and R is replaced with a C, where X is the methylation site of interest. For example, the non-bisulfite-modified sequence corresponding to SEQ ID NO: 1 provided herein is a modified version of SEQ ID NO: 1 in which each U and R in SEQ ID NO: 1 is replaced with a C, where X is the methylation site of interest; the non-bisulfite-modified sequence corresponding to SEQ ID NO:2 provided herein is a modified version of SEQ ID NO:2 in which each U and R in SEQ ID NO:2 is replaced with a C, where X is the methylation site of interest; the non-bisulfite-modified sequence corresponding to SEQ ID NO:3 provided herein is a modified version of SEQ ID NO:3 in which each U and R in SEQ ID NO:3 is replaced with a C, where X is the methylation site of interest, and so on.

TABLE-US-00001 TABLE 1 Uracil level in Uracil level in Uracil level in reacted thyroid reacted thyroid reacted thyroid nodule DNA nodule DNA nodule DNA SEQ SEQ from cancer from benign from benign ID NO: ID NO: Chromosome Chr tissues is above tissues is above tissues is below Forward Reverse (chr) Position indicated level* indicated level* indicated level* Strand Strand chr1 2996653 N/A 88.84 N/A 1 2 chr1 11979164 89.29 N/A N/A 3 4 chr1 12655938 N/A N/A 69.23 5 6 chr1 16450525 70.00 N/A N/A 7 8 chr1 16450542 72.00 N/A N/A 7 8 chr1 16450545 73.33 N/A N/A 7 8 chr1 16469987 80.00 N/A N/A 9 10 chr1 17494491 86.00 N/A N/A 11 12 chr1 25473203 88.89 N/A N/A 13 14 chr1 27640460 N/A 80.56 N/A 15 16 chr1 29565080 N/A N/A 60.00 17 18 chr1 38493013 86.36 N/A N/A 19 20 chr1 38493030 79.17 N/A N/A 19 20 chr1 38493074 80.95 N/A N/A 19 20 chr1 46713777 N/A N/A 73.33 21 22 chr1 46914121 N/A N/A 60.00 23 24 chr1 46955744 N/A N/A 77.78 25 26 chr1 55008344 N/A N/A 60.00 27 28 chr1 109816092 80.77 N/A N/A 29 30 chr1 109816111 80.77 N/A N/A 29 30 chr1 110074669 75.00 N/A N/A 31 32 chr1 110074681 71.43 N/A N/A 31 32 chr1 110074685 63.16 N/A N/A 31 32 chr1 150949856 89.29 N/A N/A 33 34 chr1 150949857 88.46 N/A N/A 33 34 chr1 153540282 78.26 N/A N/A 35 36 chr1 155162704 84.21 N/A N/A 37 38 chr1 155162714 88.64 N/A N/A 37 38 chr1 156676611 N/A N/A 84.62 39 40 chr1 157611881 83.05 N/A N/A 41 42 chr1 182205324 77.50 N/A N/A 43 44 chr1 204118999 59.09 N/A N/A 45 46 chr1 206741875 83.33 N/A N/A 47 48 chr1 206741989 66.67 N/A N/A 49 50 chr1 212587673 N/A N/A 80.00 51 52 chr1 212841198 85.29 N/A N/A 53 54 chr1 223403952 79.17 N/A N/A 55 56 chr1 233430972 N/A N/A 86.67 57 58 chr1 234342767 76.67 N/A N/A 59 60 chr10 3929071 88.68 N/A N/A 61 62 chr10 30047012 86.84 N/A N/A 63 64 chr10 79702989 83.33 N/A N/A 65 66 chr10 87984905 86.36 N/A N/A 67 68 chr10 94838789 63.33 N/A N/A 69 70 chr10 102131187 90.00 N/A N/A 71 72 chr10 104196489 75.00 N/A N/A 73 74 chr10 111766879 89.47 N/A N/A 75 76 chr10 112258886 81.82 N/A N/A 77 78 chr10 112258984 83.33 N/A N/A 79 80 chr10 112259015 82.61 N/A N/A 79 80 chr10 116391763 N/A N/A 75.00 81 82 chr10 120011530 79.55 N/A N/A 83 84 chr10 126172714 N/A 80.00 N/A 85 86 chr10 126172747 N/A 84.62 N/A 85 86 chr11 556355 N/A N/A 75.00 87 88 chr11 821282 89.13 N/A N/A 89 90 chr11 12188937 83.33 N/A N/A 91 92 chr11 12188948 77.78 N/A N/A 91 92 chr11 12188995 78.57 N/A N/A 93 94 chr11 36057726 N/A 79.63 N/A 95 96 chr11 48070143 N/A 84.38 N/A 97 98 chr11 48070163 N/A 87.50 N/A 97 98 chr11 48070166 N/A 84.38 N/A 97 98 chr11 48070174 N/A 84.48 N/A 97 98 chr11 65158294 78.00 N/A N/A 99 100 chr11 65158342 85.00 N/A N/A 99 100 chr11 65297089 75.00 N/A N/A 101 102 chr11 66104481 81.58 N/A N/A 103 104 chr11 66104485 83.33 N/A N/A 103 104 chr11 66104578 81.82 N/A N/A 105 106 chr11 68608767 N/A N/A 73.33 107 108 chr11 70236292 89.29 N/A N/A 109 110 chr11 70236320 85.71 N/A N/A 109 110 chr11 70236331 70.83 N/A N/A 109 110 chr11 115530032 N/A N/A 79.49 111 112 chr11 117950310 79.55 N/A N/A 113 114 chr11 117950329 79.55 N/A N/A 113 114 chr11 117950361 80.00 N/A N/A 115 116 chr11 117950362 81.82 N/A N/A 115 116 chr11 119293593 N/A N/A 60.00 117 118 chr12 679803 86.84 N/A N/A 119 120 chr12 26039132 73.91 N/A N/A 121 122 chr12 31004558 N/A N/A 81.82 123 124 chr12 45610695 N/A N/A 83.33 125 126 chr12 45610701 N/A N/A 86.67 125 126 chr12 45610702 N/A N/A 89.47 125 126 chr12 45610706 N/A N/A 80.00 125 126 chr12 50286016 82.14 N/A N/A 127 128 chr12 52243258 82.00 N/A N/A 129 130 chr12 52243286 82.50 N/A N/A 129 130 chr12 54145732 N/A N/A 82.35 131 132 chr12 54145741 N/A N/A 76.47 131 132 chr12 54145825 N/A N/A 70.59 131 132 chr12 56115043 89.29 N/A N/A 133 134 chr12 66262229 72.22 N/A N/A 135 136 chr12 66262230 71.74 N/A N/A 135 136 chr12 66262233 68.27 N/A N/A 135 136 chr12 66262234 71.74 N/A N/A 135 136 chr12 77266621 N/A 73.53 N/A 137 138 chr12 117580102 84.62 N/A N/A 139 140 chr12 123435962 63.89 N/A N/A 141 142 chr12 123436011 71.88 N/A N/A 143 144 chr12 123436065 69.44 N/A N/A 143 144 chr12 123540893 77.27 N/A N/A 145 146 chr13 20735797 N/A N/A 82.35 147 148 chr13 23500419 N/A N/A 68.42 149 150 chr13 46771519 67.65 N/A N/A 151 152 chr13 46771520 73.91 N/A N/A 151 152 chr13 53313426 N/A N/A 60.00 153 154 chr13 113807393 N/A N/A 27.27 155 156 chr14 38599118 65.91 N/A N/A 157 158 chr14 69170010 86.36 N/A N/A 159 160 chr14 75701632 68.42 N/A N/A 161 162 chr14 75701643 68.75 N/A N/A 161 162 chr14 90850454 N/A N/A 54.55 163 164 chr14 97524282 N/A 88.89 N/A 165 166 chr14 103541602 N/A N/A 52.00 167 168 chr14 103768055 76.09 N/A N/A 169 170 chr14 104209000 N/A 80.77 N/A 171 172 chr14 104209068 N/A 83.33 N/A 171 172 chr14 104354645 72.92 N/A N/A 173 174 chr14 104360487 83.33 N/A N/A 175 176 chr15 41068807 69.12 N/A N/A 177 178 chr15 61152225 83.33 N/A N/A 179 180 chr15 61152253 86.67 N/A N/A 181 182 chr15 61152313 86.67 N/A N/A 183 184 chr15 65186440 N/A N/A 55.56 185 186 chr15 68851629 N/A N/A 63.64 187 188 chr15 70667596 83.33 N/A N/A 189 190 chr15 70767206 90.00 N/A N/A 191 192 chr15 75251486 N/A N/A 60.00 193 194 chr15 77984014 N/A 88.89 N/A 195 196 chr15 77989064 73.53 N/A N/A 197 198 chr15 83952081 N/A N/A 72.73 199 200 chr15 85402496 82.10 N/A N/A 201 202 chr15 85402497 79.49 N/A N/A 201 202 chr15 99417337 88.89 N/A N/A 203 204 chr16 1231873 86.36 N/A N/A 205 206 chr16 1458639 N/A N/A 75.00 207 208 chr16 3023231 N/A 84.00 N/A 209 210 chr16 23135832 87.50 N/A N/A 211 212 chr16 29616265 85.71 N/A N/A 213 214 chr16 31009547 84.00 N/A N/A 215 216 chr16 31009548 85.00 N/A N/A 215 216 chr16 31009590 85.00 N/A N/A 215 216 chr16 57793674 80.95 N/A N/A 217 218 chr16 57793715 85.71 N/A N/A 217 218 chr16 57793727 80.95 N/A N/A 217 218 chr16 70771056 68.75 N/A N/A 219 220 chr16 70771079 63.33 N/A N/A 219 220 chr16 70771141 65.79 N/A N/A 219 220 chr16 77332010 72.58 N/A N/A 221 222 chr16 78540378 75.76 N/A N/A 223 224 chr16 79333435 N/A 89.61 N/A 225 226 chr16 84262419 87.23 N/A N/A 227 228 chr16 88701114 N/A N/A 66.67 229 230 chr16 89988308 N/A N/A 83.33 231 232 chr16 89988644 N/A N/A 47.37 233 234 chr17 1509928 N/A 88.46 N/A 235 236 chr17 1509945 N/A 88.46 N/A 235 236 chr17 1509952 N/A 83.93 N/A 235 236 chr17 1509953 N/A 85.00 N/A 235 236 chr17 7644013 N/A 85.42 N/A 237 238 chr17 16323460 85.00 N/A N/A 239 240 chr17 16323473 84.21 N/A N/A 239 240 chr17 16924561 80.36 N/A N/A 241 242 chr17 16924562 75.71 N/A N/A 241 242 chr17 16924594 75.71 N/A N/A 241 242 chr17 17717918 72.73 N/A N/A 243 244 chr17 17718591 84.38 N/A N/A 245 246 chr17 18139506 82.81 N/A N/A 247 248 chr17 35278031 N/A N/A 28.42 249 250 chr17 39677570 71.88 N/A N/A 251 252 chr17 40826257 N/A N/A 23.81 253 254 chr17 43037426 N/A N/A 33.33 255 256 chr17 43200096 77.78 N/A N/A 257 258 chr17 43200239 85.00 N/A N/A 259 260 chr17 43510142 N/A N/A 81.82 261 262 chr17 47987828 N/A N/A 69.23 263 264 chr17 48178379 83.33 N/A N/A 265 266 chr17 48596391 N/A 88.64 N/A 267 268 chr17 48764165 88.89 N/A N/A 269 270 chr17 55701962 68.75 N/A N/A 271 272 chr17 73584599 N/A N/A 60.00 273 274 chr17 73993165 90.00 N/A N/A 275 276 chr17 75827716 78.57 N/A N/A 277 278 chr17 76882243 61.54 N/A N/A 279 280 chr17 78765910 88.71 N/A N/A 281 282 chr17 79544478 83.15 N/A N/A 283 284 chr17 80696474 60.00 N/A N/A 285 286 chr18 19751759 N/A N/A 33.33 287 288 chr18 21440760 67.86 N/A N/A 289 290 chr18 45555437 66.18 N/A N/A 291 292 chr18 45555438 73.68 N/A N/A 291 292 chr18 46547891 76.09 N/A N/A 293 294 chr18 55888885 75.47 N/A N/A 295 296 chr18 56452096 90.00 N/A N/A 297 298 chr18 56452476 81.82 N/A N/A 299 300 chr18 56887181 N/A N/A 60.00 301 302 chr18 76002973 81.58 N/A N/A 303 304 chr18 77331090 81.03 N/A N/A 305 306 chr19 677895 85.29 N/A N/A 307 308 chr19 884044 76.92 N/A N/A 309 310 chr19 884059 76.92 N/A N/A 309 310 chr19 884105 84.62 N/A N/A 311 312 chr19 884115 84.62 N/A N/A 311 312 chr19 1136511 86.96 N/A N/A 313 314 chr19 1177605 73.68 N/A N/A 315 316 chr19 1177612 72.73 N/A N/A 315 316 chr19 1177640 81.82 N/A N/A 315 316 chr19 1860601 88.46 N/A N/A 317 318 chr19 1860607 82.81 N/A N/A 317 318 chr19 2503954 90.00 N/A N/A 319 320 chr19 3434917 N/A N/A 40.00 321 322 chr19 3434921 N/A N/A 42.86 321 322 chr19 3434930 N/A N/A 57.14 321 322 chr19 3434939 N/A N/A 71.43 321 322 chr19 3434952 N/A N/A 71.43 321 322 chr19 3434954 N/A N/A 60.00 321 322 chr19 3434962 N/A N/A 71.43 321 322 chr19 3434964 N/A N/A 71.43 321 322 chr19 3434979 N/A N/A 66.67 321 322 chr19 3434985 N/A N/A 55.56 321 322 chr19 4052713 85.56 N/A N/A 323 324 chr19 4052714 85.14 N/A N/A 323 324 chr19 4052749 84.62 N/A N/A 323 324 chr19 4374591 82.14 N/A N/A 325 326 chr19 5013982 N/A 83.33 N/A 327 328 chr19 5048836 11.21 N/A N/A 329 330 chr19 5048867 70.59 N/A N/A 329 330 chr19 5048877 73.53 N/A N/A 329 330 chr19 8367279 75.00 N/A N/A 331 332 chr19 8428573 N/A N/A 75.00 333 334 chr19 10254577 76.25 N/A N/A 335 336 chr19 10254578 79.17 N/A N/A 335 336 chr19 10463956 N/A 86.73 N/A 337 338 chr19 10464137 N/A 89.29 N/A 339 340 chr19 13203671 75.86 N/A N/A 341 342

chr19 13266925 N/A N/A 66.67 343 344 chr19 13266934 N/A N/A 66.67 343 344 chr19 13266970 N/A N/A 63.64 343 344 chr19 13842142 N/A N/A 76.47 345 346 chr19 14248494 N/A N/A 73.91 347 348 chr19 15375465 72.22 N/A N/A 349 350 chr19 17218912 81.25 N/A N/A 351 352 chr19 17346702 N/A N/A 85.71 353 354 chr19 17346702 N/A N/A 78.95 353 354 chr19 18157161 88.24 N/A N/A 355 356 chr19 18157221 86.76 N/A N/A 357 358 chr19 18157258 65.22 N/A N/A 359 360 chr19 18415877 N/A N/A 47.83 361 362 chr19 18415890 N/A N/A 47.83 361 362 chr19 30606642 80.56 N/A N/A 363 364 chr19 35531842 N/A N/A 83.33 365 366 chr19 44303112 N/A N/A 77.78 367 368 chr19 47173037 N/A 88.64 N/A 369 370 chr19 47316268 76.67 N/A N/A 371 372 chr19 47778278 N/A N/A 66.67 373 374 chr19 47778298 N/A N/A 83.33 373 374 chr2 3454277 N/A 84.78 N/A 375 376 chr2 8793724 N/A 78.57 N/A 377 378 chr2 20412441 85.71 N/A N/A 379 380 chr2 42329402 N/A N/A 78.95 381 382 chr2 42329494 N/A N/A 60.00 381 382 chr2 55289272 N/A 75.00 N/A 383 384 chr2 65064865 64.71 N/A N/A 385 386 chr2 70823641 79.03 N/A N/A 387 388 chr2 73143689 N/A N/A 77.78 389 390 chr2 74454110 70.00 N/A N/A 391 392 chr2 122014529 N/A 86.36 N/A 393 394 chr2 128158884 85.00 N/A N/A 395 396 chr2 128158910 77.50 N/A N/A 395 396 chr2 203114171 79.63 N/A N/A 397 398 chr2 218221671 N/A 85.19 N/A 399 400 chr2 219745335 N/A N/A 81.82 401 402 chr2 238341465 86.36 N/A N/A 403 404 chr2 238341542 90.00 N/A N/A 405 406 chr2 238341546 87.50 N/A N/A 405 406 chr2 238774763 67.57 N/A N/A 407 408 chr20 31126186 87.50 N/A N/A 409 410 chr20 31126189 84.21 N/A N/A 409 410 chr20 34206950 N/A N/A 76.47 411 412 chr20 36771969 79.31 N/A N/A 413 414 chr20 48993661 80.00 N/A N/A 415 416 chr20 58406398 89.66 N/A N/A 417 418 chr20 61976049 87.93 N/A N/A 419 420 chr20 61976073 89.66 N/A N/A 419 420 chr20 62588571 N/A N/A 50.00 421 422 chr20 62588579 N/A N/A 38.46 421 422 chr22 19738127 70.59 N/A N/A 423 424 chr22 35965176 76.32 N/A N/A 425 426 chr22 36549809 83.33 N/A N/A 427 428 chr22 36973375 80.43 N/A N/A 429 430 chr22 37447953 N/A N/A 73.33 431 432 chr22 37914998 N/A N/A 69.23 433 434 chr22 38307317 N/A 89.66 N/A 435 436 chr22 39662794 84.62 N/A N/A 437 438 chr22 45622980 85.00 N/A N/A 439 440 chr3 13323642 N/A N/A 72.73 441 442 chr3 14180153 57.89 N/A N/A 443 444 chr3 45209073 N/A N/A 60.00 445 446 chr3 45209207 N/A N/A 83.33 447 448 chr3 52525100 79.41 N/A N/A 449 450 chr3 62589658 87.50 N/A N/A 451 452 chr3 65388317 71.43 N/A N/A 453 454 chr3 65388388 79.31 N/A N/A 455 456 chr3 73599302 85.11 N/A N/A 457 458 chr3 195636893 N/A N/A 84.62 459 460 chr3 197093846 80.00 N/A N/A 461 462 chr4 3743223 68.18 N/A N/A 463 464 chr4 5755716 85.48 N/A N/A 465 466 chr4 5755717 80.00 N/A N/A 465 466 chr4 5755728 82.26 N/A N/A 465 466 chr4 5755729 79.17 N/A N/A 465 466 chr4 5755734 79.17 N/A N/A 465 466 chr4 8372861 N/A 85.71 N/A 467 468 chr4 57548289 80.23 N/A N/A 469 470 chr5 1118280 73.08 N/A N/A 471 472 chr5 34564389 89.29 N/A N/A 473 474 chr5 73871907 89.47 N/A N/A 475 476 chr5 78013596 70.00 N/A N/A 477 478 chr5 78013643 80.00 N/A N/A 479 480 chr5 137802650 72.73 N/A N/A 481 482 chr5 139051189 84.09 N/A N/A 483 484 chr5 167838221 68.18 N/A N/A 485 486 chr5 177541401 N/A N/A 69.23 487 488 chr5 180018672 N/A N/A 72.73 489 490 chr5 180101026 N/A N/A 64.71 491 492 chr6 3394325 N/A 87.84 N/A 493 494 chr6 3887581 N/A 85.71 N/A 495 496 chr6 7236568 84.43 N/A N/A 497 498 chr6 7728692 N/A N/A 73.33 499 500 chr6 34203617 N/A N/A 45.45 501 502 chr6 37751320 N/A N/A 78.57 503 504 chr6 41410682 N/A N/A 77.78 505 506 chr6 41438516 N/A N/A 39.13 507 508 chr6 41438575 89.66 N/A N/A 507 508 chr6 43464150 75.76 N/A N/A 509 510 chr6 158734279 N/A 86.84 N/A 511 512 chr7 989235 76.67 N/A N/A 513 514 chr7 2673543 82.14 N/A N/A 515 516 chr7 73508602 N/A N/A 85.71 517 518 chr7 105079565 78.75 N/A N/A 519 520 chr7 105079631 71.25 N/A N/A 519 520 chr7 151425103 86.96 N/A N/A 521 522 chr7 151425104 76.19 N/A N/A 521 522 chr8 11764017 80.77 N/A N/A 523 524 chr8 21647308 N/A N/A 71.43 525 526 chr8 22548399 N/A 88.16 N/A 527 528 chr8 22548483 N/A 87.50 N/A 527 528 chr8 133570537 N/A 80.00 N/A 529 530 chr8 141320393 75.00 N/A N/A 531 532 chr8 141320410 85.00 N/A N/A 531 532 chr9 6566568 86.84 N/A N/A 533 534 chr9 16197862 N/A 86.36 N/A 535 536 chr9 34591313 N/A N/A 80.00 537 538 chr9 98225096 N/A N/A 22.22 539 540 chr9 126126741 86.11 N/A N/A 541 542 chr9 132083428 N/A N/A 70.59 543 544 chr9 136077410 73.91 N/A N/A 545 546 chr9 139655018 83.33 N/A N/A 547 548 chr9 140205985 75.00 N/A N/A 549 550 chr9 140205985 83.33 N/A N/A 549 550 chr9 140205997 79.17 N/A N/A 549 550 *Level values provided are the proportion (percentage) of reacted thyroid nodule DNA molecules having a uracil at the methylation site of interest. When amplicons generated from reacted thyroid nodule DNA molecules (e.g., by PCR) are used to assess the level of methylation, the values provided correspond to the proportion of amplicons having a thymidine at the nucleotide position that corresponds to the methylation site of interest.

[0084] In embodiments, the method of detecting methylation or unmethylation of a thyroid nodule DNA of a subject detects an alteration in methylation including increase or loss of uracil level at plurality of methylation sites. In embodiments, the method of detecting methylation or unmethylation of a thyroid nodule DNA of a subject detects an alteration in methylation including increase or loss of thymidine level at plurality of methylation sites. The indicated levels in Tables 1, 2, 3, and 4, are approximate indicated levels, and include values that are within about 15%, about 10%, or about 5% above and below the indicated levels.

[0085] In embodiments, the method detects the uracil level above about a threshold as set forth in Table 2 in subjects with a cancerous thyroid nodule. In embodiments, the method detects the thymidine level above about a threshold as set forth in Table 2 in subjects with a cancerous thyroid nodule.

TABLE-US-00002 TABLE 2 Methylation Threshold for Cancerous Thyroid Nodule Uracil level in reacted thyroid nodule DNA from Chromosomal cancer tissues is about Chromosome Position above indicated level* chr1 11979164 89.29 chr1 16450525 70.00 chr1 16450542 72.00 chr1 16450545 73.33 chr1 16469987 80.00 chr1 17494491 86.00 chr1 25473203 88.89 chr1 38493013 86.36 chr1 38493030 79.17 chr1 38493074 80.95 chr1 109816092 80.77 chr1 109816111 80.77 chr1 110074669 75.00 chr1 110074681 71.43 chr1 110074685 63.16 chr1 150949856 89.29 chr1 150949857 88.46 chr1 153540282 78.26 chr1 155162704 84.21 chr1 155162714 88.64 chr1 157611881 83.05 chr1 182205324 77.50 chr1 204118999 59.09 chr1 206741875 83.33 chr1 206741989 66.67 chr1 212841198 85.29 chr1 223403952 79.17 chr1 234342767 76.67 chr10 3929071 88.68 chr10 30047012 86.84 chr10 79702989 83.33 chr10 87984905 86.36 chr10 94838789 63.33 chr10 102131187 90.00 chr10 104196489 75.00 chr10 111766879 89.47 chr10 112258886 81.82 chr10 112258984 83.33 chr10 112259015 82.61 chr10 120011530 79.55 chr11 821282 89.13 chr11 12188937 83.33 chr11 12188948 77.78 chr11 12188995 78.57 chr11 65158294 78.00 chr11 65158342 85.00 chr11 65297089 75.00 chr11 66104481 81.58 chr11 66104485 83.33 chr11 66104578 81.82 chr11 70236292 89.29 chr11 70236320 85.71 chr11 70236331 70.83 chr11 117950310 79.55 chr11 117950329 79.55 chr11 117950361 80.00 chr11 117950362 81.82 chr12 679803 86.84 chr12 26039132 73.91 chr12 50286016 82.14 chr12 52243258 82.00 chr12 52243286 82.50 chr12 56115043 89.29 chr12 66262229 72.22 chr12 66262230 71.74 chr12 66262233 68.27 chr12 66262234 71.74 chr12 117580102 84.62 chr12 123435962 63.89 chr12 123436011 71.88 chr12 123436065 69.44 chr12 123540893 77.27 chr13 46771519 67.65 chr13 46771520 73.91 chr14 38599118 65.91 chr14 69170010 86.36 chr14 75701632 68.42 chr14 75701643 68.75 chr14 103768055 76.09 chr14 104354645 72.92 chr14 104360487 83.33 chr15 41068807 69.12 chr15 61152225 83.33 chr15 61152253 86.67 chr15 61152313 86.67 chr15 70667596 83.33 chr15 70767206 90.00 chr15 77989064 73.53 chr15 85402496 82.10 chr15 85402497 79.49 chr15 99417337 88.89 chr16 1231873 86.36 chr16 23135832 87.50 chr16 29616265 85.71 chr16 31009547 84.00 chr16 31009548 85.00 chr16 31009590 85.00 chr16 57793674 80.95 chr16 57793715 85.71 chr16 57793727 80.95 chr16 70771056 68.75 chr16 70771079 63.33 chr16 70771141 65.79 chr16 77332010 72.58 chr16 78540378 75.76 chr16 84262419 87.23 chr17 16323460 85.00 chr17 16323473 84.21 chr17 16924561 80.36 chr17 16924562 75.71 chr17 16924594 75.71 chr17 17717918 72.73 chr17 17718591 84.38 chr17 18139506 82.81 chr17 39677570 71.88 chr17 43200096 77.78 chr17 43200239 85.00 chr17 48178379 83.33 chr17 48764165 88.89 chr17 55701962 68.75 chr17 73993165 90.00 chr17 75827716 78.57 chr17 76882243 61.54 chr17 78765910 88.71 chr17 79544478 83.15 chr17 80696474 60.00 chr18 21440760 67.86 chr18 45555437 66.18 chr18 45555438 73.68 chr18 46547891 76.09 chr18 55888885 75.47 chr18 56452096 90.00 chr18 56452476 81.82 chr18 76002973 81.58 chr18 77331090 81.03 chr19 677895 85.29 chr19 884044 76.92 chr19 884059 76.92 chr19 884105 84.62 chr19 884115 84.62 chr19 1136511 86.96 chr19 1177605 73.68 chr19 1177612 72.73 chr19 1177640 81.82 chr19 1860601 88.46 chr19 1860607 82.81 chr19 2503954 90.00 chr19 4052713 85.56 chr19 4052714 85.14 chr19 4052749 84.62 chr19 4374591 82.14 chr19 5048836 77.27 chr19 5048867 70.59 chr19 5048877 73.53 chr19 8367279 75.00 chr19 10254577 76.25 chr19 10254578 79.17 chr19 13203671 75.86 chr19 15375465 72.22 chr19 17218912 81.25 chr19 18157161 88.24 chr19 18157221 86.76 chr19 18157258 65.22 chr19 30606642 80.56 chr19 47316268 76.67 chr2 20412441 85.71 chr2 65064865 64.71 chr2 70823641 79.03 chr2 74454110 70.00 chr2 128158884 85.00 chr2 128158910 77.50 chr2 203114171 79.63 chr2 238341465 86.36 chr2 238341542 90.00 chr2 238341546 87.50 chr2 238774763 67.57 chr20 31126186 87.50 chr20 31126189 84.21 chr20 36771969 79.31 chr20 48993661 80.00 chr20 58406398 89.66 chr20 61976049 87.93 chr20 61976073 89.66 chr22 19738127 70.59 chr22 35965176 76.32 chr22 36549809 83.33 chr22 36973375 80.43 chr22 39662794 84.62 chr22 45622980 85.00 chr3 14180153 57.89 chr3 52525100 79.41 chr3 62589658 87.50 chr3 65388317 71.43 chr3 65388388 79.31 chr3 73599302 85.11 chr3 197093846 80.00 chr4 3743223 68.18 chr4 5755716 85.48 chr4 5755717 80.00 chr4 5755728 82.26 chr4 5755729 79.17 chr4 5755734 79.17 chr4 57548289 80.23 chr5 1118280 73.08 chr5 34564389 89.29 chr5 73871907 89.47 chr5 78013596 70.00 chr5 78013643 80.00 chr5 137802650 72.73 chr5 139051189 84.09 chr5 167838221 68.18 chr6 7236568 84.43 chr6 41438575 89.66 chr6 43464150 75.76 chr7 989235 76.67 chr7 2673543 82.14 chr7 105079565 78.75 chr7 105079631 71.25 chr7 151425103 86.96 chr7 151425104 76.19 chr8 11764017 80.77 chr8 141320393 75.00 chr8 141320410 85.00 chr9 6566568 86.84 chr9 126126741 86.11 chr9 136077410 73.91 chr9 139655018 83.33 chr9 140205985 75.00 chr9 140205989 83.33 chr9 140205997 79.17 *Level values provided are the proportion (percentage) of reacted thyroid nodule DNA molecules having a uracil at the methylation site of interest. When amplicons generated from reacted thyroid nodule DNA molecules (e.g., by PCR) are used to assess the level of methylation, the values provided correspond to the proportion of amplicons having a thymidine at the nucleotide position that corresponds to the methylation site of interest.

[0086] In embodiments, the uracil level is above a threshold as set forth in Table 3 in subjects with benign thyroid nodules. In embodiments, the thymidine level is above a threshold as set forth in Table 3 in subjects with benign thyroid nodules.

TABLE-US-00003 TABLE 3 Threshold for Benign Thyroid Nodule Uracil level in reacted thyroid nodule DNA from benign tissues is Chromosomal about above Chromosome Position indicated level* chr1 2996653 88.84 chr1 27640460 80.56 chr10 126172714 80.00 chr10 126172747 84.62 chr11 36057726 79.63 chr11 48070143 84.38 chr11 48070163 87.50 chr11 48070166 84.38 chr11 48070174 84.48 chr12 77266621 73.53 chr14 97524282 88.89 chr14 104209000 80.77 chr14 104209068 83.33 chr15 77984014 88.89 chr16 3023231 84.00 chr16 79333435 89.61 chr17 1509928 88.46 chr17 1509945 88.46 chr17 1509952 83.93 chr17 1509953 85.00 chr17 7644013 85.42 chr17 48596391 88.64 chr19 5013982 83.33 chr19 10463956 86.73 chr19 10464137 89.29 chr19 47173037 88.64 chr2 3454277 84.78 chr2 8793724 78.57 chr2 55289272 75.00 chr2 122014529 86.36 chr2 218221671 85.19 chr22 38307317 89.66 chr4 8372861 85.71 chr6 3394325 87.84 chr6 3887581 85.71 chr6 1.59E+08 86.84 chr8 22548399 88.16 chr8 22548483 87.50 chr8 1.34E+08 80.00 chr9 16197862 86.36 *Level values provided are the proportion (percentage) of reacted thyroid nodule DNA molecules having a uracil at the methylation site of interest. When amplicons generated from reacted thyroid nodule DNA molecules (e.g., by PCR) are used to assess the level of methylation, the values provided correspond to the proportion of amplicons having a thymidine at the nucleotide position that corresponds to the methylation site of interest.

[0087] In embodiments, the uracil level is below a threshold as set forth in Table 4 in subjects with benign thyroid nodule. In embodiments, the thymidine level is below a threshold as set forth in Table 4 in subjects with benign thyroid nodule.

TABLE-US-00004 TABLE 4 Methylation Threshold for Benign Thyroid Nodule Uracil level in reacted thyroid nodule DNA from Chromosomal benign tissues is about Chromosome Position below indicated level* chr1 12655938 69.23 chr1 29565080 60.00 chr1 46713777 73.33 chr1 46914121 60.00 chr1 46955744 77.78 chr1 55008344 60.00 chr1 156676611 84.62 chr1 212587673 80.00 chr1 233430972 86.67 chr10 116391763 75.00 chr11 556355 75.00 chr11 68608767 73.33 chr11 115530032 79.49 chr11 119293593 60.00 chr12 31004558 81.82 chr12 45610695 83.33 chr12 45610701 86.67 chr12 45610702 89.47 chr12 45610706 80.00 chr12 54145732 82.35 chr12 54145741 76.47 chr12 54145825 70.59 chr13 20735797 82.35 chr13 23500419 68.42 chr13 53313426 60.00 chr13 113807393 27.27 chr14 90850454 54.55 chr14 103541602 52.00 chr15 65186440 55.56 chr15 68851629 63.64 chr15 75251486 60.00 chr15 83952081 72.73 chr16 1458639 75.00 chr16 88701114 66.67 chr16 89988308 83.33 chr16 89988644 47.37 chr17 35278031 28.42 chr17 40826257 23.81 chr17 43037426 33.33 chr17 43510142 81.82 chr17 47987828 69.23 chr17 73584599 60.00 chr18 19751759 33.33 chr18 56887181 60.00 chr19 3434917 40.00 chr19 3434921 42.86 chr19 3434930 57.14 chr19 3434939 71.43 chr19 3434952 71.43 chr19 3434954 60.00 chr19 3434962 71.43 chr19 3434964 71.43 chr19 3434979 66.67 chr19 3434985 55.56 chr19 8428573 75.00 chr19 13266925 66.67 chr19 13266934 66.67 chr19 13266970 63.64 chr19 13842142 76.47 chr19 14248494 73.91 chr19 17346702 85.71 chr19 17346735 78.95 chr19 18415877 47.83 chr19 18415890 47.83 chr19 35531842 83.33 chr19 44303112 77.78 chr19 47778278 66.67 chr19 47778298 83.33 chr2 42329402 78.95 chr2 42329494 60.00 chr2 73143689 77.78 chr2 219745335 81.82 chr20 34206950 76.47 chr20 62588571 50.00 chr20 62588579 38.46 chr22 37447953 73.33 chr22 37914998 69.23 chr3 13323642 72.73 chr3 45209073 60.00 chr3 45209207 83.33 chr3 195636893 84.62 chr5 177541401 69.23 chr5 180018672 72.73 chr5 180101026 64.71 chr6 7728692 73.33 chr6 34203617 45.45 chr6 37751320 78.57 chr6 41410682 77.78 chr6 41438516 39.13 chr7 73508602 85.71 chr8 21647308 71.43 chr9 34591313 80.00 chr9 98225096 22.22 chr9 132083428 70.59 *Level values provided are the proportion (percentage) of reacted thyroid nodule DNA molecules having a uracil at the methylation site of interest. When amplicons generated from reacted thyroid nodule DNA molecules (e.g., by PCR) are used to assess the level of methylation, the values provided correspond to the proportion of amplicons having a thymidine at the nucleotide position that corresponds to the methylation site of interest.

[0088] In embodiments, the method of detecting methylation or unmethylation of a thyroid nodule DNA is of a candidate thyroid cancer patient. In embodiments, the subject is suspected of having thyroid cancer. In embodiments, the subject has thyroid cancer.

[0089] In embodiments, the method of detecting methylation or unmethylation of a thyroid nodule DNA is based on the level of uracil as set forth Table 2, in which the uracil level above the threshold identifies the thyroid nodule as a cancerous thyroid nodule. In embodiments, the method of detecting methylation or unmethylation of a thyroid nodule DNA is based on a level of thymidine indicated in Table 2, in which the thymidine level above the threshold identifies the thyroid nodule as a cancerous thyroid nodule. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method. Non-limiting examples of quantitation methods include sequencing and microarray methods.

[0090] In embodiments, the method of detecting methylation or unmethylation of a thyroid nodule DNA is based on the level of uracil as set forth Table 3, in which the uracil level above the threshold identifies the thyroid nodule as a benign thyroid nodule. In embodiments, the method of detecting methylation or unmethylation of a thyroid nodule DNA is based on a level of thymidine indicated in Table 3, in which the thymidine level above the threshold identifies the thyroid nodule as a benign thyroid nodule. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method.

[0091] In embodiments, the method of detecting methylation or unmethylation of a thyroid nodule DNA is based on the level of uracil as set forth Table 4, in which the uracil level below the threshold identifies the thyroid nodule as a benign thyroid nodule. In embodiments, the method of detecting methylation or unmethylation of a thyroid nodule DNA is based on a level of thymidine indicated in Table 4, in which the thymidine level below the threshold identifies the thyroid nodule as a benign thyroid nodule. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method.

[0092] In embodiments, the thyroid nodule is a specimen obtained by biopsy or by surgical resection of a subject.

[0093] In embodiments, the subject has undergone thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and administration of an active agent before the subject undergoes the method of detecting methylation or unmethylation of a thyroid nodule DNA.

[0094] In embodiments, the method includes a determination of prognosis for local recurrence in thyroid cancer. In embodiments, the method includes determination of prognosis of distant recurrence of thyroid cancer.

[0095] In embodiments, the method of detecting DNA methylation level in DNA of thyroid nodule may lead to changes in therapeutic regimen for treating the subject. In embodiments a subject identified as having thyroid cancer may be treated with tyrosine kinase inhibitors.

[0096] In embodiments, the active agent administered to a subject before or after detecting the level of methylation or unmethylation is: Cabozantinib-S-Malate, Caprelsa.RTM. (Vandetanib). Cometriq.RTM. (Cabozantinib-S-Malate), Doxorubicin Hydrochloride, Lenvatinib Mesylate, Lenvima.RTM. (Lenvatinib Mesylate), Nexavar.RTM. (Sorafenib Tosylate), Sorafenib Tosylate, and/or Vandetanib.

Method of Determining Thyroid Cancer or Risk of Developing Thyroid Cancer

[0097] In an aspect, provided herein is a method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof. The method involves:

[0098] (i) isolating a thyroid nodule DNA molecule from a thyroid nodule of the subject thereby forming an isolated thyroid nodule DNA molecule;

[0099] (ii) contacting the isolated thyroid nodule DNA molecule with a bisulfite salt (such as sodium bisulfite) thereby forming a reacted thyroid nodule DNA molecule; and

[0100] (iii) detecting the presence or absence of uracil in the reacted thyroid nodule DNA molecule at a methylation site set forth in Table 1; thereby detecting the thyroid cancer in the subject.

[0101] In an aspect, provided herein is a method of detecting a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof, comprising (i) isolating a plurality of thyroid nodule DNA molecules from the thyroid nodule of the subject thereby forming a plurality of isolated thyroid nodule DNA molecules, (ii) contacting the plurality of isolated thyroid nodule DNA molecules with the bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, (iii) detecting the level of reacted thyroid nodule DNA molecules in the plurality of reacted thyroid nodule DNA molecules having a uracil at a methylation site set forth in Table 1; thereby detecting the thyroid cancer in the subject.

[0102] In an aspect, provided herein is a method of detecting a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof, comprising (i) isolating a plurality of thyroid nodule DNA molecules from the thyroid nodule of the subject thereby forming a plurality of isolated thyroid nodule DNA molecules, (ii) contacting the plurality of isolated thyroid nodule DNA molecules with the bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, (iii) detecting the presence or absence of uracil in a reacted thyroid nodule DNA molecule at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of the thyroid nodule DNA molecule of the subject.

[0103] In an aspect, provided herein is a method of detecting a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof. The method includes: (i) isolating a thyroid nodule DNA molecule from a thyroid nodule of the subject thereby forming an isolated thyroid nodule DNA molecule, (ii) contacting the isolated thyroid nodule DNA molecule with a bisulfite salt (such as sodium bisulfite) thereby forming a reacted thyroid nodule DNA molecule, (iii) amplifying the reacted thyroid nodule DNA molecule thereby forming a reacted thyroid nodule DNA amplicon molecule, (iv) detecting the presence or absence of thymidine in a reacted thyroid nodule DNA amplicon molecule at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of the thyroid nodule DNA molecule of the subject. In embodiments, contacting the isolated thyroid nodule DNA with a bisulfite salt comprises adding a solution comprising the bisulfite salt to a solution comprising the isolated single stranded DNA.

[0104] In an aspect, provided herein is a method of detecting a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof, comprising (i) isolating a plurality of thyroid nodule DNA molecules from the thyroid nodule of the subject thereby forming a plurality of isolated thyroid nodule DNA molecules, (ii) contacting the plurality of isolated thyroid nodule DNA molecules with the bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, (iii) amplifying the plurality of reacted thyroid nodule DNA molecules thereby forming a plurality of reacted thyroid nodule DNA amplicon molecules, (iv) detecting one or more thyroid nodule DNA amplicon molecules within the plurality of reacted thyroid nodule DNA amplicon molecules having a thymidine at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of the thyroid nodule DNA molecule of the subject.

[0105] In embodiments, detecting one or more thyroid nodule DNA amplicon molecules comprises detecting the level of one or more one or more thyroid nodule DNA amplicon molecules. In embodiments, detecting one or more thyroid nodule DNA amplicon molecules comprises detecting the level of reacted thyroid nodule DNA amplicon molecules in the plurality of reacted thyroid nodule DNA amplicon molecules having a thymidine at a methylation site set forth in Table 1, thereby detecting the level of methylation or unmethylation in the plurality of thyroid nodule DNA molecules of the subject.

[0106] In embodiments, detecting a level includes determining the number (e.g. quantitating) or molecules having, e.g., a thymidine or a uracil. In embodiments, detecting a level includes detecting the portion or proportion of a population or plurality of molecules having, e.g., a thymidine or a uracil.

[0107] In embodiments, contacting the isolated thyroid nodule DNA with a bisulfite salt comprises adding a solution comprising the bisulfite salt to a solution comprising the isolated thyroid nodule DNA.

[0108] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes selecting a subject that has or is at risk for developing thyroid cancer. In embodiments, the subject (a) is a woman; (b) is about 20 to about 55 years old; (c) has a mutated Ret Proto-Oncogene; (d) has a grandparent, parent, or sibling who has been diagnosed with thyroid cancer, (e) self-identifies as being Caucasian or Asian; and/or (f) has or has had breast cancer.

[0109] In embodiments, the method includes detecting methylation or unmethylation at a plurality of methylation sites set forth in Table 1. In embodiments, the plurality of methylation sites comprises at least about 2, 3, 4, 5, 10, 25, 50, 75, 80, 85, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, or 550, or 5-550 methylation sites. In embodiments, the plurality of methylation sites comprises less than about 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, 90, 85, 80, 75, 50, 25, or 10 methylation sites. In embodiments, the plurality of methylation sites is about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 50, 75, 80, 85, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, or 550, or 5-550 methylation sites. In embodiments, the plurality of methylation sites includes two or more methylation sites set forth in Table 1 and no other methylation sites.

[0110] In embodiments, a method provided herein is practiced for a subject more than once over time. In embodiments, methylation or unmethylation of thyroid nodule DNA from a subject is assessed using a method provided herein at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more times. In embodiments, the method is repeated at least once every 4, 6, 8, 12 or 18 months, or at least once every 2, 3, 4, or 5 more years.

[0111] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining alteration in methylation at a plurality of methylation sites set forth in Table 1. In embodiments, the method comprises: (i) isolating DNA from multiple cells of a thyroid nodule of the subject thereby forming a plurality of isolated thyroid nodule DNA molecules, (ii) contacting the plurality of isolated thyroid nodule DNA molecules with a bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, (iii) detecting the proportion of DNA molecules in the plurality of reacted thyroid nodule DNA molecules having a uracil at a methylation site set forth in Table 1.

[0112] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes alteration. i.e., increase or loss of uracil level at plurality of methylation sites. In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes alteration, i.e., increase or loss of thymidine level at plurality of methylation sites.

[0113] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a uracil level which is above a threshold as set forth in Table 2. In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a thymidine level which is above a threshold indicated in Table 2. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method.

[0114] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a uracil level which is above a threshold as set forth in Table 3. In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a thymidine level which is above a threshold indicated in Table 3. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method.

[0115] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a uracil level which is below a threshold as set forth in Table 4. In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a thymidine level which is below a threshold indicated in Table 4. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method.

[0116] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer involves a candidate thyroid cancer patient. In embodiments, the subject is suspected of having thyroid cancer. In embodiments, the subject has thyroid cancer.

[0117] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a uracil level in which a threshold above the threshold set forth in Table 2 identifies the thyroid nodule as a cancerous thyroid nodule. In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a thymidine level in which a threshold above the threshold indicated in Table 2 identifies the thyroid nodule as a cancerous thyroid nodule. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method.

[0118] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a uracil level in which a threshold above the threshold set forth in Table 3 identifies the thyroid nodule as a benign thyroid nodule. In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a thymidine level in which a threshold above the threshold indicated in Table 3 identifies the thyroid nodule as a benign thyroid nodule. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method.

[0119] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a uracil level in which a threshold below the threshold set forth in Table 4 identifies the thyroid nodule as a benign thyroid nodule. In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a thymidine level in which a threshold below the threshold indicated in Table 4 identifies the thyroid nodule as a benign thyroid nodule. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method.

[0120] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a uracil level in DNA of a thyroid nodule specimen obtained by biopsy or by surgical resection of a subject. In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof includes determining a thymidine level in DNA of a thyroid nodule specimen obtained by biopsy or by surgical resection of a subject.

[0121] In embodiments, the method of determining a thyroid cancer or risk of developing thyroid cancer is of a subject who has previously undergone thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and/or administration of an active agent, before the determination.

[0122] In embodiments, a subject having thyroid cancer or at risk of developing thyroid cancer was administered an active agent: Cabozantinib-S-Malate, Caprelsa (Vandetanib), Cometriq (Cabozantinib-S-Malate), Doxorubicin Hydrochloride, Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate), Nexavar (Sorafenib Tosylate). Sorafenib Tosylate, and/or Vandetanib.

[0123] In embodiments, the method of determining a thyroid cancer may lead to changes in therapeutic regimen for treating the subject. In embodiments a subject identified as having thyroid cancer may be treated with tyrosine kinase inhibitors. In embodiments, a subject identified as having thyroid cancer or being at risk of developing thyroid cancer according to a method disclosed herein is advised and/or directed to receive additional screening and/or treatment for thyroid cancer.

[0124] In embodiments, the active agent administered to a subject after determining thyroid cancer is: Cabozantinib-S-Malate, Caprelsa (Vandetanib), Cometriq (Cabozantinib-S-Malate), Doxorubicin Hydrochloride. Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate), Nexavar (Sorafenib Tosylate). Sorafenib Tosylate, and/or Vandetanib.

Method of Treating Thyroid Cancer

[0125] Also provided herein is a method of treating thyroid cancer in a subject by administering to the subject an active agent for treating thyroid cancer, in which the subject is identified for treatment by a method including isolating a thyroid nodule DNA molecule from a thyroid nodule of the subject thereby forming an isolated thyroid nodule DNA molecule; contacting the isolated thyroid nodule DNA molecule with a bisulfite salt (such as sodium bisulfite) thereby forming a reacted thyroid nodule DNA molecule; and detecting the presence or absence of uracil in the reacted thyroid nodule DNA molecule at a methylation site set forth in Table 1; thereby detecting the thyroid cancer in the subject. In embodiments, contacting the isolated thyroid nodule DNA with a bisulfite salt comprises adding a solution comprising the bisulfite salt to a solution comprising the isolated thyroid nodule DNA.

[0126] In embodiments, the method includes detecting methylation or unmethylation at a plurality of methylation sites set forth in Table 1. In embodiments, the plurality of methylation sites comprises at least about 2, 3, 4, 5, 10, 25, 50, 75, 80, 85, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, or 550, or 5-550 methylation sites. In embodiments, the plurality of methylation sites comprises less than about 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, 90, 85, 80, 75, 50, 25, or 10 methylation sites. In embodiments, the plurality of methylation sites is about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 50, 75, 80, 85, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, or 550, or 5-550 methylation sites. In embodiments, the plurality of methylation sites includes two or more methylation sites set forth in Table 1 and no other methylation sites.

[0127] In embodiments, a method provided herein is practiced for a subject more than once over time. In embodiments, methylation or unmethylation of thyroid nodule DNA from a subject is assessed using a method provided herein at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more times. In embodiments, the method is repeated at least once every 4, 6, 8, 12 or 18 months, or at least once every 2, 3, 4, or 5 more years.

[0128] In embodiments, the method of treating a thyroid cancer in a subject in need thereof includes determining alteration in methylation at a plurality of methylation sites set forth in Table 1.

[0129] In embodiments, the method of treating a thyroid cancer in a subject in need thereof includes alteration which includes increase or loss of uracil level at plurality of methylation sites.

[0130] In embodiments, the method of treating a thyroid cancer in a subject in need thereof includes determining a uracil level which is above a threshold as set forth in Table 2. In embodiments, the method of treating a thyroid cancer in a subject in need thereof includes determining a thymidine level which is above a threshold indicated in Table 2. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method.

[0131] In embodiments, the method of treating a thyroid cancer in a subject in need thereof includes determining a uracil level which is above a threshold as set forth in Table 3. In embodiments, the method of treating a thyroid cancer in a subject in need thereof includes determining a thymidine level which is above a threshold indicated in Table 3. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method.

[0132] In embodiments, the method of treating a thyroid cancer in a subject in need thereof includes determining a uracil level which is below a threshold as set forth in Table 4. In embodiments, the method of treating a thyroid cancer in a subject in need thereof includes determining a thymidine level which is below a threshold indicated in Table 4. In embodiments, the level is the proportion of molecules (e.g., in a plurality of reacted thyroid nodule DNA molecules or a plurality of reacted thyroid nodule DNA amplicons) having a uracil or thymidine as determined by a quantitation method.

[0133] In embodiments, the method of treating a thyroid cancer is in a subject who has undergone surgery, radiation therapy, radioactive iodine therapy, chemotherapy, or thyroid hormone therapy, before the detecting thyroid cancer.

[0134] In embodiments, an active agent administered to a subject for treating thyroid cancer: Cabozantinib-S-Malate, Caprelsa (Vandetanib), Cometriq (Cabozantinib-S-Malate). Doxorubicin Hydrochloride, Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate). Nexavar (Sorafenib Tosylate), Sorafenib Tosylate, and/or Vandetanib.

[0135] In embodiments, the subject has or is at risk of papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, or anaplastic thyroid cancer.

[0136] In embodiments, the method includes determining a papillary thyroid carcinoma (PTC) methylation alteration score for the subject, wherein the PTC methylation alteration score is equal to the number of methylation sites in Table 1 having a uracil level equal to or greater than the corresponding threshold level set forth in Table 2.

[0137] In embodiments, the method includes determining a PTC methylation alteration score for the subject, wherein the PTC methylation alteration score is equal to the number of methylation sites in Table 1 having a thymidine level equal to or greater than the corresponding threshold level set forth in Table 2.

[0138] In embodiments, the method includes determining a benign thyroid nodule (BTN) methylation alteration score for said subject, wherein the BTN methylation alteration score is equal to: (a) the number of methylation sites in Table 1 having a uracil level equal to or greater than the corresponding threshold level set forth in Table 3; (b) the number of methylation sites in Table 1 having a uracil level equal to or less than the corresponding threshold level set forth in Table 4; or (c) the number of methylation sites in Table 1 having a uracil level equal to or greater than the corresponding threshold level set forth in Table 3 plus the number of methylation sites in Table 1 having a uracil level equal to or less than the corresponding threshold level set forth in Table 4.

[0139] In embodiments, the method includes determining a benign thyroid nodule (BTN) methylation alteration score for said subject, wherein the BTN methylation alteration score is equal to: (a) the number of methylation sites in Table 1 having a thymidine level equal to or greater than the corresponding threshold level set forth in Table 3; (b) the number of methylation sites in Table 1 having a thymidine level equal to or less than the corresponding threshold level set forth in Table 4; or (c) the number of methylation sites in Table 1 having a thymidine level equal to or greater than the corresponding threshold level set forth in Table 3 plus the number of methylation sites in Table 1 having a thymidine level equal to or less than the corresponding threshold level set forth in Table 4.

[0140] In embodiments, the method comprises calculating a Composite Cancer Risk Score for the subject. In embodiments, the Composite Cancer Risk Score for the subject equals: [the PTC methylation alteration score for said subject]/[BTN methylation alteration score for said subject]. In embodiments, the Composite Cancer Risk Score for the subject equals: [(the PTC methylation alteration score for said subject)+1]/[(BTN methylation alteration score for said subject)+1].

[0141] In embodiments, the subject is identified as being at risk of developing thyroid cancer or diagnosed as having thyroid cancer if (a) the PTC methylation alteration score for the subject is at least 5, 6, 7, 8, 9, or 10; (b) the BTN methylation alteration score for the subject is at least 5, 6, 7, 8, 9, or 10; and/or (c) the Composite Cancer Risk Score for the subject is at least about 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3.0.

[0142] In embodiments, the subject receives treatment (e.g., is directed or advised to receive treatment) for thyroid cancer or is directed to receive additional screening for thyroid cancer if (a) the PTC methylation alteration score for the subject is at least 5, 6, 7, 8, 9, or 10; (b) the BTN methylation alteration score for the subject is at least 5, 6, 7, 8, 9, or 10; and/or (c) the Composite Cancer Risk Score for the subject is at least about 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3.0.

Target Sites for Methylation Level of Thyroid Nodule

[0143] In another aspect, provided herein is a deoxyribonucleic acid 5 to 100, 5 to 300, 5 to 300, or at least about 5, 50, 100, 150, 200, 250, 300, or more nucleotides in length including a uracil-containing sequence identical to the sequence of at least 5 contiguous nucleotides within a sequence including SEQ ID NO: 1 to SEQ ID NO:550.

[0144] SEQ ID NO: 1 to SEQ ID NO:500 are 300 bp length sequences that include the target sites (i.e., methylation sites of interest). The sequences provided are as modified after bisulfite conversion. Therefore "C" in the non-CpG context becomes "U", and C in the CpG context is designated as R or X (either "U" either "C"), where X is the target site. The DNA strands (sense and antisense) are no longer complementary after bisulfite conversion. Therefore, each DNA strand is identified with its unique sequence, and is designated as "forward" and "reverse" respectively, in Table 1.

[0145] The sequences listed in Table 1 are provided below with their respective sequence identification number.

TABLE-US-00005 SEQ ID NO: Sequence 1 TUUTTAGUUUTURGTGGRGUUAGAGTTGGTTGUUTUAGTAGRGRGTGUUUAUURGG UUUAAAGUTGTTUTGUAGUTGGTUAUTGTGGGAGAAGAGAUTGGAAAAGTTUAAAG GTGGAGAGGRGGUAGRGATUTGGAGUAUTTTTURGUAXGUTGTAAUUUUTGAGAAG AAAUAAAGAGGAAARGAGGUTGTTTAGATAATUURGGGUUUTGGTGUTTGUATTTA GAAAAATTAGGUUUTUTGAAAAATTAUAGAATTATGUTGUUAGTGTUAGGTTUUU 2 AGATAATGATGTGTUTGTGT UAUAGAUAUATUATTATUTGGGAAUUTGAUAUTGGUAGUATAATTUTGTAATTTTT UAAGAGGGUUTAATTTTTUTAAATGUAAGUAUUAGGGUURGGGATTATUTAAAUAG UUTRGTTTUUTUTTTGTTTUTTUTUAGGGGTTAUAGXGTGRGGAAAAGTGUTUUAGA TRGUTGURGUUTUTUUAUUTTTGAAUTTTTUUAGTUTUTTUTUUUAUAGTGAUUAGU TGUAGAAUAGUTTTGGGURGGGTGGGUARGRGUTAUTGAGGUAAUUAAUTUTGGRG 3 UUARGGAGGGUTAAGGAU GGGTGAUUAGTGUUAUTAAAAGUAGAGUTTGAGTTTAUTUTUATAAUUATRGGUTG TGGGUUAGAUATTTGGUTGUTTTGUAGGUAGAUUAGGUTTUURGGTGAGTUATGUT GUTTAAAATGUTGTUTGGGAARGUAGAGAAAGTUTAAAXGUUAAGARGUTGAGGA UAGUUURGUAGGTGGAUTGUUATGUURGGUTRGGUUUUTTTTTGGTUUUUAGAGTG GAUUUTTUTUUTUUUUAUAGAGGGGAGGUATUTGATGGTGGUTTUAGUAGAUAAU 4 UTGGAGAAGAAUUAUTUAGGGT AUUUTGAGTGGTTUTTUTUUAGGTTGTUTGUTGAAGUAUUATUAGATGUUTUUUU TUTGTGGGGAGGAGAAGGGTUUAUTUTGGGGAUUAAAAAGGGGURGAGURGGGUA TGGUAGTUUAUUTGRGGGGUTGTUUTUAGRGTUTTGGXGTTTAGAUTTTUTUTGRGT TUUUAGAUAGUATTTAAGUAGUATGAUTUAURGGGAAGUUTGGTUTGUUTGUAAA GUAGUUAAATGTUTGGUUUAUAGURGATGGTTATGAGAGTAAAUTUAAGUTUTGUT 5 TTTAGTGGUAUTGGTUAUUU CAGUTGGGGAGGGGAUAGGGTAGGTGGUTGUAGAAGGGGGUTGGGTTGAGGTUTU AGGTGUAGARGAGGAGGGGUTGGGRGGAGGGGGTGAGGAGGGGAGURGGGUTGGG GGURGGGRGRGUTGUTGGGGTUUUUUTUURGUUURGGGAUXGTURGUTUTTGUUUA GAUURGTRGGTAAAUAGARGURGTGATGTUARGGGRGURGUTGAUUTGTGGUTGAA UURGGAGUTGTAAATGAGATGUAAGGTGUUAGUAGUUTURGGURGUAGGGUUTAR 6 GAGUUAUARGRGUTUUTURGURGG URGGRGGAGGAGRGRGTGTGGUTRGTAGGUUUTGRGGURGGAGGUTGUTGGUAUUT TGUATUTUATTTAUAGUTURGGGTTUAGUUAUAGGTUAGRGGRGUURGTGAUATUA RGGRGTUTGTTTAURGARGGGTUTGGGUAAGAGRGGAXGGTUURGGGGRGGGAGGG GGAUUUUAGUAGRGUUURGGUUUUUAGUURGGUTUUUUTUUTUAUUUUUTURGUU UAGUUUUTUUTRGTUTGUAUUTGAGAUUTUAAUUUAGUUUUUTTUTGUAGUUAUU TAUUUTGTUUUUTUUUUAGUTG 7 TTTTUTGTAAAATGGGGURGUUUAUAAAAUTUATAAUAAAGTGTTGAGGTTURGAU AAGURGAAAUUTGTGAAAAGUTTGTGTAAAUUTUAGAGUTGTAUATGGATGGTTGA AGGATUTATTTRGAUAGUTURGGGGAGUXGTGGGAGGGAAGUTGAXGGXGGUTUTT GUTGTTUTUUTAUUTUUUAGUUUTUURGAAGAUTUTGAGUAGUUTGGAGATUAAAG GTGATTGGGGUUTGUTGGUATGGAGGURGGGUTRGGUAGAAUUTGUTTUURGGUUU UUTGUUUAUUTUUUAUUUAU 8 GTGGGTGGGAGGTGGGUAGGGGGURGGGAAGUAGGTTUTGURGAGUURGGUUTUU ATGUUAGUAGGUUUUAATUAUUTTTGATUTUUAGGUTGUTUAGAGTUTTRGGGAGG GUTGGGAGGTAGGAGAAUAGUAAGAGUXGUXGTUAGUTTUUUTUUUAXGGUTUUU RGGAGUTGTRGAAATAGATUUTTUAAUUATUUATGTAUAGUTUTGAGGTTTAUAUA AGUTTTTUAUAGGTTTRGGUTTGTRGGAAUUTUAAUAUTTGTTATGAGTTTTGTGG GRGGUUUUATTTTAUAGAAAA 9 TGAGUAGTGTTTUAGRGUUUAGAGAGAUAUTGTGGAGAAGGTUUAUUAGGATGUU TAUUTGUUTTAUAUAAGAGUUTAAUTTTGGUAUAUUTGTGGUAUAUUTGTGGAGAG UTGTTUTGGUUURGGTTGTUTGGUAGGUUTGGGUTAUTUXGAGUAGGGGAAUTGGG GUAUAGTGGUTGUAUUTURGGUTATAUUUTGGTTTTTUUAGTTUUTGATGUURGUU UUTUAGGTGGUAGUATGAGGTGAUTUAGGGAUAGARGUUUTTATRGTGARGUAAGT UUAGUUUUUAGTGGAGUUUUT 10 AGGGGUTUUAUTGGGGGUTGGAUTTGRGTUARGATAAGGGRGTUTGTUUUTGAGTU AUUTUATGUTGUUAUUTGAGGGGRGGGUATUAGGAAUTGGAAAAAUUAGGGTATA GURGGAGGTGUAGUUAUTGTGUUUUAGTTUUUUTGUTXGGAGTAGUUUAGGUUTG UUAGAUAAURGGGGUUAGAAUAGUTUTUUAUAGGTGTGUUAUAGGTGTGUUAAAG TTAGGUTUTTGTGTAAGGUAGGTAGGUATUUTGGTGGAUUTTUTUUAUAGTGTUTUT UTGGGRGUTGAAAUAUTGUTUA 11 TUTTGTAAAATTUUAGAGUUAGGTATAUUUAATrUTGUAARGTGGTAGUTGUATGA UTGTAUAAGTUUUTTAAUAGUAURGGGUUTUAGTGAUATUATUTGTTAAATGGGTT GGTGATGATAATGGTUAGUATTTATGGAGGAGUUUAUAXGGTGUTAAGTGUTTrAU AUATATUAGUTAAUTGAATUUTUAUTGUTGUUAATGAGAUAGGTAUTATTGAATUA GAGGUURGGAGAGAGUTUUARGRGGTTGGTUATAUTGGTGAAGAGUTTGGTTUAAT GUUTGGTGAAUTUTRGGUAU 12 GTGURGAGAGTTUAUUAGGUATTGAAUUAAGUTUTTUAUUAGTATGAUUAAURGRG TGGAGUTUTUTURGGGUUTUTGATTUAATAGTAUUTGTUTUATTGGUAGUAGTGAG GATTUAGTTAGUTGATATGTGTAAAGUAUTTAGUAUXGTGTGGGUTUUTUUATAAA TGUTGAUUATTATUATUAUUAAUUUATTTAAUAGATGATGTUAUTGAGGUURGGTG UTGTTAAGGGAUTTGTAUAGTUATGUAGUTAUUARGTTGUAGAATTGGGTATAUUT GGUTUTGGAATTTTAUAAGA 13 TURGGAGUUAGTGAAUTTGTGATURGGAGUUAGTTAAUTTUAUAGUTAATGTGUTG AGUAGUATTUUAGUUAGRGTUTGAAGUUAGAGUAGGGAGGRGGARGGGUUUUAGG AGTTRGAGGTURGGGAAGURGAAGUAUUAUUAAAUTGAGXGAGGTTUUAAUTUTU UUTUUUAGGAGGTURGGUTGUUTUUUAUUAGUAGUUUAAUUAUAGGGTUUTGUTU UAGARGTTAUTATTTTUTUTTTTTUAGTGTGTUUAGUAGUAAUUTRGAUTGUUAAUA AUAARGTGAAAAATAAUTGUAG 14 UTGUAGTTATTTTTUARGTTGTTGTTGGUAGTRGAGGTTGUTGUTGGAUAUAUTGAA AAAGAGAAAATAGTAARGTUTGGAGUAGGAUUUTGTGGTTGGGUTGUTGGTGGGAG GUAGURGGAUUTUUTGGGAGGGAGAGTTGGAAUUTXGUTUAGTTTGGTGGTGUTTR GGUTTUURGGAUUTRGAAUTUUTGGGGUURGTURGUUTUUTGUTUTGGUTTUAGA RGUTGGUTGGAATGUTGUTUAGUAUATTAGUTGTGAAGTTAAUTGGUTURGGATUA UAAGTTUAUTGGUTURGGA 15 TTGUUAAAAUTGGAAGUAAUUAAGATGUUUUTUAAAAGGTGAATGGAGGUUAGGT GRGGTGGUTUARGURGATAATUUUAGUAUTTTGGGAGGUTGAGGUAGGTGGATUAU TTGAGATUARGAGTTTGAGAUUAGUURGGUUAAUATGGXGAAAUUURGTUTUTAUT AAAAATAUTAAGATTAAURGGGRGTGGTGGUARGTGUUTGTTATUUUAGUTAUTTG GGAAGUTGAGGUAGGUAAATTGUTTGAAUUTGGGAGGTGGAGGTUAUAGTGAGUU AAGATTGTGUUAUTGUAUTUUA 16 TGGAGTGUAGTGGUAUAATUTTGGUTUAUTGTGAUUTUUAUUTUUUAGGTTUAAGU AATTTGUUTGUUTUAGUTTUUUAAGTAGUTGGGATAAUAGGUARGTGUUAUUARGU URGGTTAATUTTAGTATTTTTAGTAGAGARGGGGTTTXGUUATGTTGGURGGGUTGG TUTUAAAUTRGTGATUTUAAGTGATUUAUUTGUUTUAGUUTUUUAAAGTGUTGGGA TTATRGGRGTGAGUUAURGUAUUTGGUUTUUATTUAUUTTTTGAGGGGUATUTTGGT TGUTTUUAGTTTTGGUAA 17 GGRGGGATURGAGURGAGAUARGTGUTGGAGRGGAGURGUTTUUTUARGGTRGUUA GURGUAGAUAAUTGAUUTUUURGGUATRGRGTTRGRGGUUUTGUTGUTGGUTURGG TGTUTRGGGURGGAAUTUUTGTGGUTUUAGRGTTRGXGURGGUUAUTGGUUAGRGU TTGGGUUTRGUUUTGUAGUTURGGGGUUATAGGGUAUAGUTTTAGUTTTGAUUTUU URGTTUURGAAAGGARGUUUAAGGRGAUUTUUUAUUUUATUUTUUUUAAUTTUTU UUUUATGTUUTGRGGUAAUTT 18 AGTTGURGUAGGAUATGGGGGAGAAGTTGGGGAGGATGGGGTGGGAGGTRGUUTTG GGRGTUUTTTRGGGAARGGGGAGGTUAAAGUTAAAGUTGTGUUUTATGGUUURGGA GUTGUAGGGRGAGGUUUAAGRGUTGGUUAGTGGURGGXGRGAARGUTGGAGUUAU AGGAGTTURGGUURGAGAUAURGGAGUUAGUAGUAGGGURGRGAARGRGATGURG GGGAGGTUAGTTGTUTGRGGUTGGRGAURGTGAGGAAGRGGUTURGUTUUAGUARG TGTUTRGGUTRGGATUURGUUU 19 UUAGUAGGGAAGGUAGUUAAUAGATGUAGAUTRGUTUTGUUTAUUTGTGGAGGUR GGTGAGGUUAGGGUUTGTTGGGAUTTGAAAUAGTGAGGUAAGTGGGTGTGTGGTGU TGGGUTUUUXGUTUAAGTTUTUUUAGXGTGUUAGTTUURGGAGUUTTATGTGUAGG GTGTTGGGGAAGGGXGGGUTGAATRGTGGGTGGGAGTUTTGGUTUAAAGUUUUAGG TGAGTGGAGGAATTGGGGGRGGAUUTGAAGTAUTGTUTTGAAGTGGAUUTGGUAGG UUTUTTGGGUTTGTGUAGUTG 20 UAGUTGUAUAAGUUUAAGAGGUUTGUUAGGTLTUAUTTUAAGAUAGTAUTTUAGGT URGUUUUUAATTUUTUUAUTUAUUTGGGGUTTTGAGUUAAGAUTUITUAUUUARGAT TUAGUUXGUUUTTUUUUAAUAUUUTGUAUATAAGGUTURGGGAAUTGGUAXGUTG GGAGAAUTTGAGXGGGGAGUUUAGUAUUAUAUAUUUAUTTGUUTUAUTGTTTUAA GTUUUAAUAGGUUUTGGUUTUAURGGUUTUUAUAGGTAGGUAGAGRGAGTUTGUA TUTGTTGGUTGUUTTUUUTGUTGG 21 UUAGAUTRGUUUTUUUUAUURGGGUUTRGGAUTTTUAUUUUAGUTTUTUTUTUUTG GUUAGTGATTAUUUAUUUUUAATUUUAUUURGUUURGURGRGUAAUTAUUTUUTU UUTTUAUURGGAUTGGGAUUATUATUUUUAUTUUAUTUXGUUUAGTUTGGGAUTU UAUUTGUUTUUTUUUUAATUUUAUAUTAATUTUTGUTTGGTUTUTTUUTUTTTGGUU TAATUTUTRGTUTRGGUTTATTGGGGARGGUUAUTUTUAUAGTTTGGTTUUAAAUAU UAGTTUUTGGATGGATTUUU 22 GGGAATUUATUUAGGAAUTGGTGTTTGGAAUUAAAUTGTGAGAGTGGURGTUUUUA ATAAGURGAGARGAGAGATTAGGUUAAAGAGGAAGAGAUUAAGUAGAGATTAGTG TGGGATTGGGGAGGAGGUAGGTGGAGTUUUAGAUTGGGXGGAGTGGAGTGGGGAT GATGGTUUUAGTURGGGTGAAGGGAGGAGGTAGTTGRGRGGRGGGGRGGGGTGGG ATTGGGGGTGGGTAATUAUTGGUUAGGAGAGAGAAGUTGGGGTGAAAGTURGAGG UURGGGTGGGGAGGGRGAGTUTGG 23 RGUAGGUURGRGUUURGUTUURGUUURGUUTGURGRGUUTUURGGGGRGUURGUA TTAAAGRGUATATGUAAGUUATGAATTATUAAUTGAAAGGAGTUAATTAURGGUTU TAAAAARGAGTGTUTGRGUTRGUAGRGUUURGGGUUATUXGUUTATTTARGGAGRG ATUTAUUURGUURGGUTGGGGAGGGGGUUTRGGGAGGGAGAGAGARGGAGAAARG GAGUURGAGAURGGGAGAGAGURGGAGAGGUAGGGAUTGGAGAGTUTGGGAUARG AAGGAGAGGRGGGGAGAGAURGA 24 TRGGTUTUTUUURGUUTUTUUTTRGTGTUUUAGAUTUTUUAGTUUUTGUUTUTURGG UTUTUTUURGGTUTRGGGUTURGTTTUTURGTUTUTUTUUUTUURGAGGUUUUUTUU UUAGURGGGRGGGGTAGATRGUTURGTAAATAGGXGGATGGUURGGGGRGUTGRG AGRGUAGAUAUTRGTTTTTAGAGURGGTAATTGAUTUUTTTUAGTTGATAATTUATG GUTTGUATATGRGUTTTAATGRGGGRGUUURGGGAGGRGRGGUAGGRGGGGRGGGA GRGGGGRGRGGGUUTGRG 25 AUAGTRGUTGUAGGGAGGARGRGGGURGTGAGAAUURGGGGAUAGUUTUUUUTUT TGRGGTUUTGUAGTUURGGAUUUAUTGGGRGGATUAGAAAGTTTGUAGGGAGUUA GGGAUTAGGAGAUAGAUAGAUAGRGUAGGGAUAGAGAAAGXGGAGGGATGUUAG AAAGAURGAGTRGGGGAUAGAUAGAGAGAUUUAGGGTGAGAUAGAGGAAGAGAT AUURGGGGUTGAAAARGGTGGUAGAAAGTGAGUAAUTTAGGGAGAUAGAAAGAGR GUAGAAUTRGAAATTURGAGGUAGAGA 26 TUTUTGUUTRGGAATTTRGAGTTUTGRGUTUTTTUTGTUTUUUTAAGTTGUTUAUTTT UTGUUAURGTTTTUAGUUURGGGTATUTUTTUUTUTGTUTUAUUUTGGGTUTUTUTG TUTGTUUURGAUTRGGTUTTTUTGGUATUUUTUXGUTTTUTUTGTUUUTGRGUTGTU TGTUTGTUTUUTAGTUUUTGGUTUUUTGUAAAUTTTUTGATURGUUUAGTGGGTURG GGAUTGUAGGAURGUAAGAGGGGAGGUTGTUUURGGGTTUTUARGGUURGRGTUU TUUUTGUAGRGAUTGT 27 TUAGUUTGTAUUURGGRGUTGGUUTUUAGAUAGUUAGGTGUTGUUTRGUARGGTUT TGUTTGUAGGUTGGGGUATGAAGUAUUUTGGTATTTARGUTGGGATTGGTUTUTUA UTAGGGTTGGGGRGGGUTGTGGTUAUUTGGUURGGRGXGURGUAGAGGUTGGUTUR GGAGAAGAUUTGGGGGRGUAAGAUTUAGAGGUUAGAGGGTGUAGURGUTGUTGAU TUATTTGRGGARGGGGRGGUTGGGAGGAGRGUTAGUUUUTGTTGTGAGRGATTTGA GAGUUAGGGUUAAATUTGGGT 28 AUUUAGATTTGGUUUTGGUTUTUAAATRGUTUAUAAUAGGGGUTAGRGUTUUTUUU AGURGUUURGTURGUAAATGAGTUAGUAGRGGUTGUAUUUTUTGGUTUTUTGAGTUT TGRGUUUUUAGGTUTTUTURGGAGUUAGUUTUTGRGGXGRGURGGGUUAGGTGAU UAUAGUURGUUUUAAUUUTAGTGAGAGAUUAATUUUAGRGTAAATAUUAGGGTGU TTUATGUUUUAGUUTGUAAGUAAGAURGTGRGAGGUAGUAUUTGGUTGTUTGGAG GUUAGRGURGGGGTAUAGGUTGA 29 GUUUAGUUTUAUAAAGGTGAGTGGGGUAUUUUUAGUTGURGAGUTUUUUTAGTUA GUAGUUTUATAUUTUAUATTUTUUTGTGGURGUAUUTUAUAGUUURGUUURGGUU UAUAGGUATUUTTAAGAAGAAGTGTUTGUUUAUUATUAGXGAGAAGAGUAGUUTU UTGXGGUTUUUUUTGGAGUAATGUAUAGGGTUTTUURGGGGUTUUTURGUTAGTGA GGGUAGURGGGGAGGUUUUUUTUUURGUUUAURGUUURGGUAGAGUUTUUAGGA GUAGUTGAARGGGGTUATGUUUATRG 30 RGATGGGUATGAUUURGTTUAGUTGUTUUTGGAGGUTUTGURGGGGRGGTGGGRGG GGAGGGGGGUUTUUURGGUTGUUUTUAUTAGRGGAGGAGUUURGGGAAGAUUUTG TGUATTGUTUUAGGGGGAGUXGUAGGAGGUTGUTUTTUTXGUTGATGGTGGGUAGA UAUTTUTTUTTAAGGATGUUTGTGGGURGGGGRGGGGUTGTGAGGTGRGGUUAUAG GAGAATGTGAGGTATGAGGUTGUTGAUTAGGGGAGUTRGGUAGUTGGGGGTGUUU UAUTUAUUTTTGTGAGGUTGGGU 31 TUAGAATAATGGUTGGTTTGTAGAGATUAGAAATGUUUAUTGUTGTTTUUTGTAT UUUTUUAUUUAUUUAGAUTGAGUUTUTGAAGUTGTURGGGGUUTGGAGAGAGAAG UUAUTUAAGGAUAGUAGUTGUTGAUTUAGAXGUTUAAATTUTXGGGXGGAAAAGG AUUTTAGAGAATGUUTAAAATRGTGGUUUAATUUUTUATTGGAAGUTGGGGUTURG AAAAGURGGGGUTURGAAAAGUTGGGAGAGUAGUUUAAAGRGTAUTGUUUAUTAA ATGTGGATGUARGUTGGAURGU 32 GRGGTUUAGRGTGUATUUAUATTTAGTGGGUAGTARGUTTTGGGUTGUTUTUUUAG UTTTTRGGAGUUURGGUTTTTRGGAGUUUUAGUTTUUAATGAGGGATTGGGUUARG ATTTTAGGUATTUTUTAAGGTUUTTTTUXGUUXGAGAATTTGAGXGTUTGAGTUAGU AGUTGUTGTUUTTGAGTGGUTTUTUTUTUUAGGUUURGGAUAGUTTUAGAGGUTUA GTUTGGGTGGGTGGAGGGATAUAGGAAAUAGUAGTGGGUATTTUTGATUTUTAUAA AUUAGGUUATTATTUTGGA 33 AAGTTUTGGGGUAGAAGTTGGATAAUUAGGGUUTGAGAAATAAAGATAAGAGGGT ATATTUUTUUUUUAGGAGAUAAAAGAGAAGGTGGATGGAGAAGGGGAAAUTGGGU UTUAGUUAGUAURGGGATGATGRGAUUAGUTTTGTUAGUAXGUTTGGGGAGUATAU AUAURGUTTGUUTTGGUTGGAURGGAGAUTGTGATUAUUAUUUTTUUAAUUUATUU UUUAAUARGUAGGUTGGUATGGUUARGUUUAUAGTGUUUUAAGTGUTGUUTGUUT TGUAGTGAUTUAUTTUUTUTGTA 34 TAUAGAGGAAGTGAGTUAUTGUAAGGUAGGUAGUAUTTGGGGUAUTGTGGGRGTG GUUATGUUAGUUTGRGTGTTGGGGGATGGGTTGGAAGGGTGGTGATUAUAGTUTUR GGTUUAGUUAAGGUAAGRGGTGTGTATGUTUUUUAAGXGTGUTGAUAAAGUTGGTR GUATUATUURGGTGUTGGUTGAGGUUUAGTTTUUUUTTUTUUATUUAUUTTUTUTTT TGTUTUUTGGGGGAGGAATATAUUUTUTTATUTTTATTTUTUAGGUUUTGGTTATUU AAUTTUTGUUUUAGAAUTT 35 TUAGAARGTGUUUAUAUATGUUUATGUUUTUTATUUTGUTGAAATUUAAUUUUUU UTTUAAAGGUUAUTGUAGGGAGUUTTUUUAGGGUUUAAURGGATTUAGTGTUTAU UTGTTUTGTUUTGTAUAAAGRGUUUUTTTTGUUUTTTTXGTGTGTAUTTAGAGAATT UTGATTTTGAUTGAATUAUUTGTGTAUTTGTTTTUTUTUAGUUTUAUUUUUAUATGG TGAGUTUAURGGTUTTAUTUATTTUTGUATGAGGTAAGGGTUTRGUUUAUAUUAGG TGUUAAUUAGTGUTTARGGU

36 URGTAAGUAUTGGTTGGUAUUTGGTGTGGGRGAGAUUUTTAUUTUATGUAGAAATG AGTAAGAURGGTGAGUTUAUUATGTGGGGGTGAGGUTGAGAGAAAAUAAGTAUAU AGGTGATTUAGTUAAAATUAGAATTUTUTAAGTAUAUAXGAAAAGGGUAAAAGGG GRGUTTTGTAUAGGAUAGAAUAGGTAGAUAUTGAATURGGTTGGGUUUTGGGAAGG UTUUUTGUAGTGGUUTTTGAAGGGGGGGTTGGATTTUAGUAGGATAGAGGGUATGG GUATGTGTGGGUARGTTUTGAA 37 UAUUTRGTGUUUUTUAUUTGTAAGUAUTGTGAGGAGUAGUAGUAGGAAGAAAGGA GAUTGGGTGUURGGTGTUATGGTGGTGGTGAAATGGGTGGGGAGGGGGUAGAAUA GATTUAGGUAGGRGUTGGUTGUTTGAGAGGTGGAGXGGGUAUAGGXGUUTAURGU TTTATAURGGTUUUUUUAUTUUURGUURGUURGUUUTAGGUAUAGURGGAGUAGG TGAUAGGTGAUAAAAUUURGUUUUUTUUUUTAUUTUUTAUUTUTTUUTUUTUUTUU UUAAUUATTUUTGGGTAGGGTAUA 38 TGTAUUUTAUUUAGGAATGGTTGGGGAGGAGGAGGAAGAGGTAGGAGGTAGGGGA GGGGGRGGGGTTTTGTUAUUTGTUAUUTGUTURGGUTGTGUUTAGGGRGGGRGGGR GGGGAGTGGGGGGAURGGTATAAAGRGGTAGGXGUUTGTGUUXGUTUUAUUTUTU AAGUAGUUAGRGUUTGUUTGAATUTGTTUTGUUUUUTUUUUAUUUATTTUAUUAUU AUUATGAUAURGGGUAUUUAGTUTUUTTTUTTUUTGUTGUTGUTAUTUAUAGTGUT TAUAGGTGAGGGGUARGAGGTG 39 AGARGGAGAAAUAGAAARGGAGGTUAGGRGGGGAGUUTRGGGGAUAGGUUTGGGA UURGAGGURGGAAAURGUAGAGGAGRGAAGUUTGGRGGGATGUAGTGATTGGAGU UAAAGGAAURGTUURGGUUTGTUUAARGRGGGGGGGUUTTXGGUURGGTGGUUUT GAGRGAAURGATGUARGTGGUUURGURGUATUUUATUUUUUAUUUTUUUUAGAUT UTUUUTUUUAGUTUUTTUTGAGGRGGAAAGAAAAAUUUTAUATUTGGTUUUAGUU UTGGGTUUUTGUUUTGGUUUUTUUT 40 AGGAGGGGUUAGGGUAGGGAUUUAGGGUTGGGAUUAGATGTAGGGTTTTTUTTTUR GUUTUAGAAGGAGUTGGGAGGGAGAGTUTGGGGAGGGTGGGGGATGGGATGRGGR GGGGUUARGTGUATRGGTTRGUTUAGGGUUAURGGGUXGAAGGUUUUUURGRGTT GGAUAGGURGGGARGGTTUUTTTGGUTUUAATUAUTGUATUURGUUAGGUTTRGUT UUTUTGRGGTTTURGGUUTRGGGTUUUAGGUUTGTUUURGAGGUTUUURGUUTGAU UTURGTTTUTGTTTUTURGTUT 41 TUAAAUUUAGGTATTUTGGGTUTAGTRGGTGTTUTTUTGUUAAAGAGTAUTTTGTGG UTAAATTUAUTGGATGTGAUTUAGTTTTTATUTTTRGTUATUTUTTAGUTTTGUUTTA TUUAAAURGGATUAUTUTUTTUTGUTTAGAAUTXGTTUTGUTUTTGGTGAUAGTGGT AUATAUTUTUATAUTGUUTUTTUUUTTGUUUAGAGTUUTTUUTTUTUATGTTUUAUU TUUTUTAUTGGGAURGGUUTGGGTGTGUTGTUUAATRGGAUAUTATTTTGTTGGGUU UTUTUUTTUAUTUU 42 GAGTGAAGGAGAGGGUUUAAUAAAATAGTGTURGATTGGAUAGUAUAUUUAGGUR GGTUUUAGTAGAGGAGGTGGAAUATGAGAAGGAAGGAUTUTGGGUAAGGGAAGAG GUAGTATGAGAGTATGTAUUAUTGTUAUUAAGAGUAGAAXGAGTTUTAAGUAGAA GAGAGTGATURGGTTTGGATAAGGUAAAGUTAAGAGATGARGAAAGATAAAAAUTG AGTUAUATUUAGTGAATTTAGUUAUAAAGTAUTUTTTGGUAGAAGAAUAURGAUTA GAUUUAGAATAUUTGGGTTTGAU 43 AAGTGTUTTTAUUTUUTGAGTGRGAUUUAAGTUAGGAGGUAGGAGGUTGAUTGAGG GAUARGGAGGAGGTATGUAUAUTUAUAGUATGAGGUAGAGUTGTGTGUAUAUATU AAGUAAGGAAATGGGGURGGAATATGGGGUAAAGGUUTAXGGATTGAATGGTGGA TTTGGATGTGGGUUAUTTUTTUUAGUUUUTGAAAGAGGAUUAGGUAATGTGGUTAT GAATGGGUUTAATGAGAATTGATTGATTRGUTRGAGATGTTTTUTTTTTUTTUUTAAA ATAGAAAATGAUATAUUUUA 44 TGGGGTATGTUATTTTUTATTTTAGGAAGAAAAAGAAAAUATUTRGAGRGAATUAAT UAATTUTUATTAGGUUUATTUATAGUUAUATTGUUTGGTUUTUTTTUAGGGGUTGG AAGAAGTGGUUUAUATUUAAATUUAUUATTUAATUXGTAGGUUTTTGUUUUATATT URGGUUUUATTTUUTTGUTTGATGTGTGUAUAUAGUTUTGUUTUATGUTGTGAGTGT GUATAUUTUUTURGTGTUUUTUAGTUAGUUTUUTGUUTUUTGAUTTGGGTRGUAUT UAGGAGGTAAAGAUAUTT 45 GGATGTGUTUAGGUTUUAGGGUUAUAUUUTGUATGTAUTUATAGUAUAGUUUATTU TGGAAGGTGUAGTAGAGTTTGGGGGUAUAGUTGTGTGUTRGUAGUAGUTGGAAGTT TUTGAUUTUATTUTUURGGTUUAUUAGUAGUTURGTUXGUTUUUUATAUAUURGGA UUAGUARGUAGTUUTGUATGTUUTUUTUUAUATAGUAGGUUAUUAGUTTGTTGGTG ATGUUATURGTGAAGRGUTAGUATGGGGAGAGGAUAGTGRGTGGGTGGGTGGGTGG GGUAGGATUTUTUTGGTUTU 46 GAGAUUAGAGAGATUUTGUUUUAUUUAUUUAUUUARGUAUTGTUUTUTUUUUATG UTAGRGUTTUARGGATGGUATUAUUAAUAAGUTGGTGGUUTGUTATGTGGAGGAGG AUATGUAGGAUTGRGTGUTGGTURGGGTGTATGGGGAGXGGARGGAGUTGUTGGTG GAURGGGAGAATGAGGTUAGAAAUTTUUAGUTGUTGRGAGUAUAUAGUTGTGUUU UUAAAUTUTAUTGUAUUTTUUAGAATGGGUTGTGUTATGAGTAUATGUAGGGTGTG GUUUTGGAGUUTGAGUAUATUU 47 AGUUAGGAAGGGUTGUAUTTUUUUAGTGGTUAGRGUAGGUTGGRGTUUTGGUTGUT GGRGUAAGTUTUAAGUTGUUUUTUUUUTTUTAGUAAGUATGGGRGGTGTGGGTATG RGGGGTGUTGGGTAUTGAUTUAUUTURGGAGAUUAUTXGGUTUUUAUAUAUUAUU TUTGAATGATUTGAATUATTTATGAGGUTGAATGUUUTGTUUTUUAGGGAGUTUUA GUTGGAGUTGGAGUUAGUATATGGAGGTGGAGAGAGUTUUXGUAGTUAUURGGGU UUTGTAUAGUUTGUAGGUAGAAU 48 GTTUTGUUTGUAGGUTGTAUAGGGUURGGGTGAUTGXGGGAGUTUTUTUUAUUTUU ATATGUTGGUTUUAGUTUUAGUTGGAGUTUUUTGGAGGAUAGGGUATTUAGUUTUA TAAATGATTUAGATUATTUAGAGGTGGTGTGTGGGAGUXGAGTGGTUTURGGAGGT GAGTUAGTAUUUAGUAUUURGUATAUUUAUAURGUUUATGUTTGUTAGAAGGGGA GGGGUAGUTTGAGAUTTGRGUUAGUAGUUAGGARGUUAGUUTGRGUTGAUUAUTG GGGAAGTGUAGUUUTTUUTGGUT 49 GGGTGUTGGGTAUTGAUTUAUUTURGGAGAUUAUTXGGUTUUUAUAUAUUAUUTU TGAATGATUTGAATUATTTATGAGGUTGAATGUUUTGTUUTUUAGGGAGUTUUAGU TGGAGUTGGAGUUAGUATATGGAGGTGGAGAGAGUTUUXGUAGTUAUURGGGUUU TGTAUAGUUTGUAGGUAGAAUUTATAAAUTGGAUTUUTAAAGUUAUTUUTUTUAAG GUUTGGAGATTUTGUTGAGTTTUAUTUTITGGUTUTUAGAGUATUTGGAAUTUTAUA TAAAGUTGAGGAAUUUTTTGT 50 AUAAAGGGTTUUTUAGUTTTATGTAGAGTTUUAGATGUTUTGAGAGUUAAAGAGTG AAAUTUAGUAGAATUTUUAGGUUTTGAGAGGAGTGGUTTTAGGAGTUUAGTTTATA GGTTUTGUUTGUAGGUTGTAUAGGGUURGGGTGAUTGXGGGAGUTUTUTUUAUUTU UATATGUTGGUTUUAGUTUUAGUTGGAGUTUUUTGGAGGAUAGGGUATTUAGUUTU ATAAATGATTUAGATUATTUAGAGGTGGTGTGTGGGAGUXGAGTGGTUTURGGAGG TGAGTUAGTAUUUAGUAUUU 51 AGTUUATGAAGGUAUTTTTTUAAAGTTAGGTGGTUAUUAAAAAAUAGGTAATUAAT UUTGTUAUUAGURGRGGGGAUAGRGAGGUUTTGGGUTTGGAGGGGGAGGATGURG ARGATGURGAURGRGUATUAGATUTRGURGGGAGGAGGGXGRGGGRGUTUUAUTTG TTGUAAAGAARGURGGGTTUUTUTGGGUUATTGGGUTGURGUTURGGRGGGGAGRG RGGAAGGUTGGGUUTUAGGTAGUTTUAATUATTUAUUTGUTGGTTARGGGTRGRGG RGURGGGGAUUUTAUTURGGA 52 TURGGAGTAGGGTUUURGGRGURGRGAUURGTAAUUAGUAGGTGAATGATTGAAGU TAUUTGAGGUUUAGUUTTURGRGUTUUURGURGGAGRGGUAGUUUAATGGUUUAG AGGAAUURGGRGTTUTTTGUAAUAAGTGGAGRGUURGXGUUUTUUTUURGGRGAGA TUTGATGRGRGGTRGGUATRGTRGGUATUUTUUUUUTUUAAGUUUAAGGUUTRGUT GTUUURGRGGUTGGTGAUAGGATTGATTAUUTGTTTTTTGGTGAUUAUUTAAUTTTG AAAAAGTGUUTTUATGGAUT 53 GTUTGUAGUTGGGAATGAATGGAATGAAGGTUAAGGATGAAGTAATAAUUAAATAT TGGGTTTTGGGTGUUUTGGTAAUTGTURGGTTTUUAGTTAGGGTTUUTGGGTGAUAT UTTUUTTUTGGGGGAAGAUAGAGTUAAATGAGAAAXGTGAGTTGAGUUUAGGGGA AAGGATUATURGGGAGATGUUTGAGGGGUTUUAGGGUATRGTAATUTUTTGUTUAG UTGGUAGAGTGGGGUTGAUARGGUUAGUTGUTUTUTGGAGTUUTRGGUUTTUUTGT TTUUUUUTGAGGAUTTTGAG 54 TUAAAGTUUTUAGGGGGAAAUAGGAAGGURGAGGAUTUUAGAGAGUAGUTGGURG TGTUAGUUUUAUTUTGUUAGUTGAGUAAGAGATTARGATGUUUTGGAGUUUUTUA GGUATUTUURGGATGATUUTTTUUUUTGGGUTUAAUTUAXGTTTUTUATTTGAUTUT GTUTTUUUUUAGAAGGAAGATGTUAUUUAGGAAUUUTAAUTGGAAAURGGAUAGT TAUUAGGGUAUUUAAAAUUUAATATTTGGTTATTAUTTUATUUTTGAUUTTUATTUU ATTUATTUUUAGUTGUAGAUA 55 UUAGTGUAGAAUAGGUAUTGUUUAUUATAUAGGUUAGAAGAGGTGUUUTUTUUAU AUTGGUUAUTGAAAUTAUTUAUTGGUAGUAGTGGGTGUUAUTTGGAAAAUAAGAT GGUUUTUUUTGUAGAGUAGGUUAUUUTGURGGAGGTGTUUXGATGRGTGTGAAGU AGGGTTGGAGGUAUAUTAUAGGUAUTUTUTAGTUUTTUAAAUAAUAUTGTAGTGTA GATUTTGTTGGTTUTTTUAGAGAAGGGGAAARGGAAAUTUAUAGAAGUAAUTAGAG GAGTGAGTAGAAGUUUAGGTATG 56 UATAUUTGGGUTTUTAUTUAUTUUTUTAGTTGUTTUTGTGAGTTTURGTTTU UTUTGAAAGAAUUAAUAAGATUTAUAUTAUAGTGTTGTTTGAAGGAUTAGAGAGTG UUTGTAGTGTGUUTUUAAUUUTGUTTUAUARGUATXGGGAUAUUTURGGUAGGGTG GUUTGmWGUAGGGAGGGUUATUTTGTTTTUUAAGTGGUAUUUAUTGUTGUUAGT GAGTAGTTTUAGTGGUUAGTGTGGAGAGGGUAUUTUTTUTGGUUTGTATGGTGGGU AGTGUUTGTTUTGUAUTGG 57 TURGGUATUAATTUTTAATGAGTUUURGAGUUUURGUAGTUUGTUTAUTTUTTTTU TTTTUUAGTGAATUUTUAUAGTUUUUTTTUUUTGUATGTTUTUTGTUUUAAATTTUT GAAGUUUUTUUUTTTURGTUTUTTAAGAATUTUTAXGAAUURGAAAGUURGTGAGG UTGATGGUARGTUTGTGGTTUUTTTUTUUTTUTTUUUTUUATAUUUAUAGUTUUURG GGAURGGAUUUTUUUUAUTUAUUAGGTGUAGGGUUAGGGGUAGUAGUAGGAGGA AUAGUUAUAGGTAGAGGTG 58 UAUUTUTAUUTGTGGUTGTTUUTUUTGUTGUTGUUUUTGGUUUTGUAUUTGGTGAG TGGGGAGGGTURGGTUURGGGGAGUTGTGGGTATGGAGGGAAGAAGGAGAAAGGA AUUAUAGARGTGUUATUAGUUTUARGGGUTTTRGGGTTXGTAGAGATTUTTAAGAG ARGGAAAGGGAGGGGUTTUAGAAATTTGGGAUAGAGAAUATGUAGGGAAAGGGGA UTGTGAGGATTUAUTGGAAAAGAAAAGAAGTAGAUAGGAUTGRGGGGGUTRGGGG AUTUATTAAGAATTGATGURGGA 59 AGUUTGTGUTUAGGAATAAUTAAGGAGTGGAGURGUATUAAUUTUUTTUUUAAATU RGGARGTUTTUUTURGAUTUAAGUUUAGUUTGAGGGUUATTUTUUTTGATTUAUUU TTGGAAAUAGAUAUUAGUUAAGGGAGUTGTUTUUTGGXGTTGARGAGGATURGATT TAGGTUAGTATTUTAGTTUUUAUTUUAUAGAGGAATUTGAUTGGAGGUUAGUTGTG GTRGATGAGTUATURGGAAUAUAAGUAGGUAGUTATTTURGAAUTAAATGGUATUT GATUTUUUTUUTUAUUTTGA 60 TUAAGGTGAGGAGGGAGATUAGATGUUATTTAGTTRGGAAATAGUTGUUTGUTTGT GTTURGGATGAUTUATRGAUUAUAGUTGGUUTUUAGTUAGATTUUTUTGTGGAGTG GGAAUTAGAATAUTGAUUTAAATRGGATUUTRGTUAAXGUUAGGAGAUAGUTUUUT TGGUTGGTGTUTGTTTUUAAGGGTGAATUAAGGAGAATGGUUUTUAGGUTGGGUTT GAGTRGGAGGAAGARGTURGGATTTGGGAAGGAGGTTGATGRGGUTUUAUTUUTTA GTTATTUUTGAGUAUAGGUT 61 GAUUTUAGGATUTGAATGGTTUTTGGAGTTUTTTGUAGATGAGGTAATGTTTTGGTT AAUTUATAGGTUAGAUUTGUTGTUUTTAGUTAAUTTGUURGGGAGGTTTTTAARGG AAGGUUTGTGTTAGUAUAAATUATATTTUUTGATGAXGAGUAGAGAUITITGATUTG GTUTTAAAGAARGRGTTTTUUAAUTTAUUUTGGGAUTTTTTTGAATTAGURGGUUAU ATATAUUAGGGTTUTUAGAGGATTTTTTUTUUUUTTTUTUTUTGTUTUTTTUTGGG TTTUUTATTAUTAATT 62 ATTAGTAATAGGAAAAAUUUAGAAAGAGAUAGAGAGAAAGGGGGGAAAAAATUUT UTGAGAAUUUTGGTATATGTGGURGGUTAATTUAAAAAAGTUUUAGGGTAAGTTGG AAAARGRGTTUTTTAAGAUUAGATUAAGGTUTUTGUTXGTUATUAGGAAATATGAT TTGTGUTAAUAUAGGUUTTURGTTAAAAAUUTUURGGGUAAGTTAGUTAAGGAUAG UAGGTUTGAUUTATGAGTTAAUUAAAAUATTAUUTUATUTGUAAAGAAUTUUAAGA AUUATTUAGATUUTGAGGTUU 63 GUUTGGAAUUURGGRGATUTUTTGTTTUTUUAUUAAGGGAAUTUTGUTTGTAAUAU TTTAAGUUTUAGUTGAAAAGTGGTUTUUTGGGTGAAGTUTUAUUTGTGUAUUUAUU TGAGGGTGAGTUAGUTUTGUTUUUUTGGUTUTUAURGXGGUTGTTATAGUATTTAU RGGAGTUUUAUAGTGAUTUATTTGTUUATUAUUUTUURGAUAAAUUTTUUAGUTTU TGAAGGGUAGAGAUAGUATUATAATUATUTTTTATAAUTUURGTGUUTAGTGUTAU TUUUAATUUUTAGTAAGUAT 64 ATGUTTAUTAGGGATTGGGAGTAGUAUTAGGUARGGGAGTTATAAAAGATGATTAT GATGUTGTUTUTGUUUTTUAGAAGUTGGAAGGTTTGTRGGGAGGGTGATGGAUAAA TGAGTUAUTGTGGGAUTURGGTAAATGUTATAAUAGUXGRGGTGAGAGUUAGGGGA GUAGAGUTGAUTUAUUUTUAGGTGGGTGUAUAGGTGAGAUTTUAUUUAGGAGAUU AUTTTTUAGUTGAGGUTTAAAGTGTTAUAAGUAGAGTTUUUTTGGTGGAGAAAUAA GAGATRGURGGGGTTUUAGGU 65 AATUUUTTUUURGGGATAGTUAARGAGGUTTTUAATTTAAAUTTGUATTTGAAGUTT GUAGAGAUTUAUAUTGAUTTAUUUAGGUUUTAAUAUAUAGUAGUTGTUTUUATGG TTGRGUUAGGTAGTGAAGGATAUAGGGUAGUAGGAAAXGAGTUURGGTTUTUAGGT GGATUURGTGUTTUUAUUTUTGTTAGAGUUUAGGUUUTGAGGGUATAGGGUUAAAT TGUUAUAGAGUTUUAGAGAAATUTGTUTUTUURGTUUUUUAUUUTAAGAUTGAGUT GUTGGAGGAAAGAGGUUAGG 66 UUTGGUUTUTTTUUTUUAGUAGUTUAGTUTTAGGGTGGGGGARGGGAGAGAUAGAT TTUTUTGGAGUTUTGTGGUAATTTGGUUUTATGUUUTUAGGGUUTGGGUTUTAAUA GAGGTGGAAGUARGGGATUUAUUTGAGAAURGGGAUTXGTTTUUTGUTGUUUTGTA TUUTTUAUTAUUTGGRGUAAUUATGGAGAUAGUTGUTGTGTGTTAGGGUUTGGGTA AGTUAGTGTGAGTUTUTGUAAGUTTUAAATGUAAGTTTAAATTGAAAGUUTRGTTGA UTATUURGGGGAAGGGATT 67 AGGAATGTTTAUTGAAGGAGTGAATGAAAUTATTGUATTAGATUAAGUUUAGGTGU AGAGGAUTGGTTTUAUATAGAAAGUATRGATTTTGUUUTAUAGAAUUUTGAUTUUA GTTTTUUAGUAGAUAAUUUTGGTGTGAAGAUAGAGGGGXGGGGAGGAAGGTAGGG GUTGAUATTTUUUAGUUUUTUUUAGGURGGTGGGGAGUTGAATAGUTUAGTGAUTT GTUUAGGAGUURGAGGTAAAUUAUAGAUTAAGAGUUAAGAGTUATGATTUAUTAU TTGUATTTUTUUAGUUATGAUA 68 TGTUATGGUTGGAGAAATGUAAGTAGTGAATUATGAUTUTTGGUTUTTAGTUTGTGG TTTAUUTRGGGUTUUTGGAUAAGTUAUTGAGUTATTUAGUTUUUUAURGGUUTGGG AGGGGUTGGGAAATGTUAGUUUUTAUUTTUUTUUUXGUUUUTUTGTUTTUAUAUUA GGGTTGTUTGUTGGAAAAUTGGAGTUAGGGTTUTGTAGGGUAAAATRGATGUTTTUT ATGTGAAAUUAGTUUTUTGUAUUTGGGUTTGATUTAATGUAATAGTTTUATTUAUTU UTTUAGTAAAUATTUUT 69 GUTGGGATTATATATGUAUAUUAUUATGUURGGUTAATTTTTATATTTTTGGTAGAG ATAGGGGTTUUAUUATGTTGGUUAGGGTGGTUTTGAAUUUUTGAUUTUAGGTGATU UAUUUAUUTTGGUUTUUUAGAGTGUTGGGATTAUAGGXGTGAGUUAUTGUAUURG GUAUAAAGUUATTTTAAAAUAGUTTTTTTTTTTTTTTTGAAAUAGUUTTGUUUTGTA GUUUAGGUTGGAGTGTAGTGGTAUAATUTUAGUTUAUTGUAAUUTUUAUUTTURGG GTTUAAGTGATTUTTGTGU 70 GUAUAAGAATUAUTTGAAUURGGAAGGTGGAGGTTGUAGTGAGUTGAGATTGTAUU AUTAUAUTUUAGUUTGGGUTAUAGGGUAAGGUTGTTTUAAAAAAAAAAAAAAAGU TGTTTTAAAATGGUTTTGTGURGGGTGUAGTGGUTUAXGUUTGTAATUUUAGUAUTU TGGGAGGUUAAGGTGGGTGGATUAUUTGAGGTUAGGGGTTUAAGAUUAUUUTGGU UAAUATGGTGGAAUUUUTATUTUTAUUAAAAATATAAAAATTAGURGGGUATGGTG GTGTGUATATATAATUUUAGU 71 AAUAAATGUUAUAGGUUUTAATTGUAGGUTUUAAGGAGTTGAGATTUUATAUTGGG GTTGUTGGAGGUAGAAGUUTTUUUAUTTTUAGGAUURGGAUUTGUUUTTUUUUUAR GRGGTUURGUUUAGUUAGUTAUAUUUTGGUUAUAGAGXGUTUAUAAAGGUTUAGT GTGTGTATGURGGGUTGAUTUAUAGTGGTTUTGGGUUUAGGRGAGGAUUTTUTUAG AGGGGRGGAAGGGGUUUTUTUUUTUUTGGUUATTTTUUATGGGGAGUAGTUAGTAA UUAGGAUUATGUUAGAUTTUA

72 TGAAGTUTGGUATGGTUUTGGTTAUTGAUTGUTUUUUATGGAAAATGGUUAGGAGG GAGAGGGUUUUTTURGUUUUTUTGAGAAGGTUUTRGUUTGGGUUUAGAAUUAUTG TGAGTUAGUURGGUATAUAUAUAUTGAGUUTTTGTGAGXGUTUTGTGGUUAGGGTG TAGUTGGUTGGGRGGGAURGRGTGGGGGAAGGGUAGGTURGGGTUUTGAAAGTGG GAAGGUTTUTGUUTUUAGUAAUUUUAGTATGGAATUTUAAUTUUTTGGAGUUTGUA ATTAGGGUUTGTGGUATTTGTT 73 GUAGTGUTAUAAUATUAATGUUAAGGURGTGGGGUAGUTGATGGTTTGGGUTUUUA AUTTUUUAGUUAGGTGUTTUTGUAGGUUUAUATUTTGUUUAUTGGUUAAAUUTTTA AATAAUTTTGAUTRGGGUTAUTUTTATGUTUAAAGAXGTUAGGGGUTUTUUUAAAT UTUTTTAUUUTGUUAGAAAGTUTTUTATAGTARGGUUTUUAUTTAGUTTTUARGUUT GATUTTUUATRGUATUUTGUTUATAAUUTGUUAUTAGTGAAUUUUTGUTGUTURGG UTUUAUAUTTUTUATGUTG 74 AGUATGAGAAGTGTGGAGURGGAGUAGUAGGGGTTUAUTAGTGGUAGGTTATGAG UAGGATGRGATGGAAGATUAGGRGTGAAAGUTAAGTGGAGGURGTAUTATAGAAG AUTTTUTGGUAGGGTAAAGAGATTTGGGAGAGUUUUTGAXGTUTTTGAGUATAAGA GTAGUURGAGTUAAAGTTATTTAAAGGTTTGGUUAGTGGGUAAGATGTGGGUUTGU AGAAGUAUUTGGUTGGGAAGTTGGGAGUUUAAAUUATUAGUTGUUUUARGGUUTT GGUATTGATGTTGTAGUAUTGUU 75 AGGAGGGARGTGGAAGTRGTGGGTGGUAGAGAAAAGTGTGUAURGUTGGGAGGTU TATTTUAAGAATAGGTTGGGATGAGAAAUATGTUTGGGRGAGGGGGGTGGGAGGUU RGGTGTUAUUTGTGGATGGATUUAUAGUUUTGUAATTGXGTGTTGUAAAGTTTGUU RGGUUURGUATTUATTTTGAAGGTTUTTGGRGATGUUTRGAUTTTTRGUUTUAAAGA AGTGAGUTUTUATAAGGTTUAGAGGURGGGAGUUAAAGRGGGAGTGAAGAUTUTR GAGGGGTUUAAATGAAGUAGA 76 TUTGUTTUATTTGGAUUUUTRGAGAGTUTTUAUTUURGUTTTGGUTUURGGUUTUTG AAUUTTATGAGAGUTUAUTTUTTTGAGGRGAAAAGTRGAGGUATRGUUAAGAAUUT TUAAAATGAATGRGGGGURGGGUAAAUTTTGUAAUAXGUAATTGUAGGGUTGTGGA TUUATUUAUAGGTGAUAURGGGUUTUUUAUUUUUUTRGUUUAGAUATGTTTUTUAT UUUAAUUTATTUTTGAAATAGAUUTUUUAGRGGTGUAUAUTTTTUTUTGUUAUUUA RGAUTTUUARGTUUUTUUT 77 UUTTTTTGAUUTGGRGAGTUUUTTUUUTTTUUATTTUATTTTATTGUTTTTTATTGTTT UUUTURGGUUTUTTUTUUUUTUUTAGGTUTTTTUTUTAGUTUAGTTTGGAGUTUAUA TUUTTTUUAUUUTTTTUAUUTUUTUUTTUUTUXGUUUUAGGATTATUUUTGGGAUU UATUUTGAGUTGAGUUTAUAGUUAGUUAGUUARGAAATAGAGGTGRGRGGGGGUA GGGTGGTATGGAGATTUTGXGGUUTTTGATTTGAUAUUTUURGGAGUTAURGUUAU AGGUUTGUUUATTTUAU 78 TGAAATGGGUAGGUUTGTGGRGGTAGUTURGGGAGGTGTUAAATUAAAGGUXGUA GAATUTUUATAUUAUUUTGUUUURGRGUAUUTUTATTTRGTGGUTGGUTGGUTGTA GGUTUAGUTUAGGATGGGTUUUAGGGATAATUUTGGGGXGGAGGAAGGAGGAGGT GAAAAGGGTGGAAAGGATGTGAGUTUUAAAUTGAGUTAGAGAAAAGAUUTAGGAG GGGAGAAGAGGURGGAGGGAAAUAATAAAAAGUAATAAAATGAAATGGAAAGGGA AGGGAUTRGUUAGGTUAAAAAGGU 79 GUTUAGTTTGGAGUTUAUATUUTTTUUAUUUTTTTUAUUTUUTUUTTUUTUXGUUUU AGGATTATUUUTGGGAUUUATUUTGAGUTGAGUUTAUAGUUAGUUAGUUARGAAA TAGAGGTGRGRGGGGGUAGGGTGGTATGGAGATTUTGXGGUUTTTGATTTGAUAUU TUURGGAGUTAUXGUUAUAGGUUTGUUUATTTUAUUTGURGGGAAGATAAUTTTGG UTTUTGGTGGTGGGTGGGTGATTGAUTUTUAAAATUUAAAGUATTGGTTTITTUTGG GTTAUTTUUTATGAUTGUT 80 AGUAGTUATAGGAAGTAAUUUAGAAAAAAUUAATGUTTTGGATTTTGAGAGTUAAT UAUUUAUUUAUUAUUAGAAGUUAAAGTTATUTTUURGGUAGGTGAAATGGGUAGU UUTGTGGXGGTAGUTURGGGAGGTGTUAAATUAAAGGUXGUAGAATUTUUATAUU AUUUTGUUUURGRGUAUUTUTATTTRGTGGUTGGUTGGUTGTAGGUTUAGUTUAGG ATGGGTUUUAGGGATAATUUTGGGGXGGAGGAAGGAGGAGGTGAAAAGGGTGGAA AGGATGTGAGUTUUAAAUTGAGU 81 UATTUUAAUTTUTGUAAUUATGUAUAGTGATRGATATTTATAATTAUUTTTTTUUTT UAUUATGGUAAURGGGTUUTURGARGAGUAGGAUTGAAGAAGGAARGAGGAATAA AUTUTGGGAGTGGAAGRGRGUUTRGGUAGAUAGATURGXGGGRGUTGGGGUAGUU AGGAGAAGUUURGGUATURGUTTGTGAGGTURGGGGUTGTGGTUTRGAGTUURGUU URGUUTRGGRGGGUUURGUTUUUATGUURGUUURGUTATRGUUUURGRGUTUTTUT URGUURGUURGURGAGUTGUA 82 TGUAGUTRGGRGGGRGGGRGGAGAAGAGRGRGGGGGRGATAGRGGGGRGGGUATG GGAGRGGGGUURGURGAGGRGGGGRGGGAUTRGAGAUUAUAGUUURGGAUUTUAU AAGRGGATGURGGGGUTTUTUUTGGUTGUUUUAGRGUUXGRGGATUTGTUTGURGA GGRGRGUTTUUAUTUUUAGAGTTTATTUUTRGTTUUTTUTTUAGTUUTGUTRGTRGG AGGAUURGGTTGUUATGGTGAAGGAAAAAGGTAATTATAAATATRGATUAUTGTGU ATGGTTGUAGAAGTTGGAATG 83 TATGATGUUAGTGGTTGAATAUUTTAGTAGAGAAAAATUTTGAATAATUAAUKUUA GGTTUAGGAGAUAGUTGGGTATTTGAGAGUUTATGAGTUAUATAAGUAAUUTTGGA GUUAAGTTGTATTUTUTGTTTGGUUTUAGAGUUAGTUTXGAGUAUATGUAGUUAGA UTGURGGUAGAGAAGATGTGGAGUTGGUATTUTGGUTTAGGUUTGAGUAAGGTRGT GGAAGUUUUAGGTTUUTGAUUATGGUURGUAUAGAGUUATGUTUUAGUUUTGGGT UTUAGUAGGUAGUUAGGTGAG 84 UTUAUUTGGUTGUUTGUTGAGAUUUAGGGUTGGAGUATGGUTUTGTGRGGGUUATG GTUAGGAAUUTGGGGUTTUUARGAUUTTGUTUAGGUUTAAGUUAGAATGUUAGUT UUAUATUTTUTUTGURGGUAGTLTTGGUTGUATGTGUTXGAGAUTGGUTUTGAGGUU AAAUAGAGAATAUAAUTTGGUTUUAAGGTTGUTTATGTGAUTUATAGGUTUTUAAA TAUUUAGUTGTUTUUTGAAUUTURGGTTGATTATTUAAGATTTTTUTUTAUTAAGGT ATTUAAUUAUTGGUATUATA 85 GGGGUTRGUAGTGGUUTAGTUTGUTUTGGGUTTTGUTGGATGUUUTTRGAGAATUA URGRGUAAUUTUUTTUAGAGGUUUAAUAUTUUARGTGUTGAUTTUURGGGUUTGTG TUTUUUUTGURGUAGAUTGAAGXGTTUURGGUTGAAGGTGAGGTTUTGUAUUAAXG AGTRGUAGAAGTUURGGGUAGAGUTGGTGGGGUAGUTTUAGAGGUTGGGATTTGAU ATUTUTGAGUAGGAGGTGAURGUUURGGUAUUAGUTGUUTGUUAGATUUTGAAGG AGUAAGGUUTGRGAUUATAUU 86 GGTATGGTRGUAGGUUTTGUTUUTTUAGGATUTGGUAGUUAGUTUUUUKUUUUKU GTUAUUTUUTGUTUAGAGATGTUAAATUUUAGUUTUTGAAGUTGUUUUAUUAGUTU TGUURGGGAUTTUTGRGAUTXGTTGGTGUAGAAUUTUAUUTTUAGURGGGAAXGUT TUAGTUTGRGGUAGGGGAGAUAUAGGUURGGGAAGTUAGUARGTGGAGTGTTGGG UUTUTGAAGGAGGTTGRGRGGTGATTUTRGAAGGGUATUUAGUAAAGUUUAGAGU AGAUTAGGUUAUTGRGAGUUUU 87 GRGGGGUUAGUAGRGTGUURGGRGGGAAGRGGTAUAGGRGUTURGGGAAGURGRG UAUUAGUTGUTTUAGUAUUATGURGUTUAGGTRGGURGTGUTUTUUTGRGARGGGT TGAAGATGRGGARGAAUTTUTUURGGUAGUTUAUAGUUAXGATUTTUAGGUUTGTR GGGUTGGGAAGAGAGGAGARGUTGTGAGGAGATGRGGURGGTUUAUURGUAUAGU TGRGRGUUURGUURGGAAAUUAGUTUUAGTURGGRGURGGAGGUTTGGGTUAUTRC UUUUTTAUUTUTGUAGGAGTTU 88 GAAUTUUTGUAGAGGTAAGGGGRGAGTGAUUUAAGUUTURGGRGURGGAUTGGAG UTGGTTTURGGGRGGGGRGRGUAGUTGTGRGGGTGGAURGGURGUATUTUUTUAUA GRGTUTUUTUTUTTUUUAGUURGAUAGGUUTGAAGATXGTGGUTGTGAGUTGURGG GAGAAGTTRGTURGUATUTTUAAUURGTRGUAGGAGAGUARGGURGAUUTGAGRGG UATGGTGUTGAAGUAGUTGGTGRGRGGUTTUURGGAGRGUUTGTAURGUTTUURGU RGGGUARGUTGUTGGUUURGU 89 AGGAGTGTTTGGGGTGUTTUUTUTTGGUTGUAGTGGGAUAUAGGTGTGUUTTUUTA GGAAUTGGGUUUTGAUTAUTTUUAGUUUAAUAUTUURGGGUUTGTGAAUTGTGAU UTGTGTGURGGGATGGGTTTTGTGGGTUTGUUUUATUUUXGUAUTGUTGGATUTGG UUAAGTGGGTGAAGGUTAAGGURGGTUAGAGTTGAGTTTUTGUUTTGTUUUUTUTU UTGGGUTAGATGUUAUAUUAGGUUUAGTGAUTUATAGGGUAGGUAGTTGGGAAAT AUUAGGUAGAGGGUAGGTUUTG 90 UAGGAUUTGUUUTUTGUUTGGTATTTUUUAAUTGUUTGUUUTATGAGTUAUTGGGU UTGGTGTGGUATUTAGUUUAGGAGAGGGGAUAAGGUAGAAAUTUAAUTUTGAURG GUUTTAGUUTTUAUUUAUTTGGUUAGATUUAGUAGTGXGGGGATGGGGUAGAUUU AUAAAAUUUATUURGGUAUAUAGGTUAUAGTTUAUAGGUURGGGAGTGTTGGGUT GGAAGTAGTUAGGGUUUAGTTUUTAGGAAGGUAUAUUTGTGTUUUAUTGUAGUUA AGAGGAAGUAUUUUAAAUAUTUUT 91 GUAGGAATUAGGUUAGRGTATGTAATGAAAAUTUTTGRGTTATUTTTTTAGAAGGAT GTGAUTGTATTTTATGAGTATGUAGUAGGGTUAUUAUAUAUUTTTTGUTUUTGGGU UUUTUUUUTGTGTGTAGUUUAGGUUURGGTTTGTGUTXGAGGGUUAGAXGGUUUTA TGGTUUUUAGTTTUUTURGTAGATUAUAUAGGGAGGUAGRGAGGUAGGGTGUAAG GATGTTAGGGGTGGAAGGGGTGAUAURGGGAGUAAAGAUTGUTAUUUUTTGGUUT GGATAAAUUTGTUTGAUATTU 92 GAATGTUAGAUAGGTTTATUUAGGUUAAGGGGTAGUAGTUTTTGUTUURGGTGTUA UUUUTTUUAUUUUTAAUATUUTTGUAUUUTGUUTRGUTGUUTUUUTGTGTGATUTA RGGAGGAAAUTGGGGAUUATAGGGURGTUTGGUUUTXGAGUAUAAAUXGGGGUUT GGGUTAUAUAUAGGGGAGGGGUUUAGGAGUAAAAGGTGTGTGGTGAUUUTGUTGU ATAUTUATAAAATAUAGTUAUATUUTTUTAAAAAGATAARGUAAGAGTTTTUATTA UATARGUTGGUUTGATTUUTGU 93 TGAUTGTATTTTATGAGTATGUAGUAGGGTUAUUAUAUAUUTTTTGUTUUTGGGUU UUTUUUUTGTGTGTAGUUUAGGUUURGGTTTGTGUTRGAGGGUUAGARGGUUUTAT GGTUUUUAGTTTUUTURGTAGATUAUAUAGGGAGGUAGXGAGGUAGGGTGUAAGG ATGTTAGGGGTGGAAGGGGTGAUAURGGGAGUAAAGAUTGUTAUUUUTTGGUUTG GATAAAUUTGTUTGAUATTUURGAUUTUTGAAGTUATUUATUATGGUTGRGUTGGU TUAGAUAUTTUAAGGGUUAUTTT 94 AAAGTGGUUUTTGAAGTGTUTGAGUUAGRGUAGUUATGATGGATGAUTTUAGAGGT RGGGAATGTUAGAUAGGTTTATUUAGGUUAAGGGGTAGUAGTUTTTGUTUURGGTG TUAUUUUTTUUAUUUUTAAUATUUTTGUAUUUTGUUTXGUTGUUTUUUTGTGTGAT UTARGGAGGAAAUTGGGGAUUATAGGGURGTUTGGUUUTRGAGUAUAAAURGGGG UUTGGGUTAUAUAUAGGGGAGGGGUUUAGGAGUAAAAGGTGTGTGGTGAUUUTGU TGUATAUTUATAAAATAUAGTUA 95 UAUAUAUUTTTUAGTTGAGGGGRGUTGAGGTUUUTGUTGTTGUTGTGURGTUTGAU UTGTUUUUTUTUTUTGAUAGAGAGUUAGUTGUTUUURGGGAAUAAUTTUAUUAATG AGTGUAAUATAUUAGGUAAUTTUATGTGUAGUAATGGAXGGTGUATUURGGGRGU UTGGUAGTGTGARGGGUTGUUTGAUTGUTTRGAUAAGAGTGATGAGAAGGAGTGUR GTGAGTGGUUTGGUUUTTTGUTGGGGTGGGGTGGUAGUUATUUTGGGGUAGAGGGG AGUAGGTUUTGAGUAGGUTTA 96 TAAGUUTGUTUAGGAUUTGUTUUUUTUTGUUUUAGGATGGUTGUUAUUUUAUUUU AGUAAAGGGUUAGGUUAUTUARGGUAUTUUTTUTUATUAUTUTTGTRGAAGUAGTU AGGUAGUURGTUAUAUTGUUAGGRGUURGGGATGUAUXGTUUATTGUTGUAUATG AAGTTUUTGGTATGTTGUAUTUATTGGTGAAGTTGTTUURGGGGAGUAGUTGGUTU TUTGTUAGAGAGAGGGGAUAGGTUAGARGGUAUAGUAAUAGUAGGGAUUTUAGRG UUUUTUAAUTGAAAGGTGTGTG 97 UATGUATTTTGTGTTTGTAGTGTGUTGGUUARGGGAGUAUTUTAAAUAUATTATGGG URGGGRGUAGTGGUTURGGUUTGTAATUTUAGUAUTTTGGGAGGUTGAGGRGGGUA GATUAUTTGAGUUUAGGAGTTXGAUAUUAGUUTGGUUAAUAXGGXGAAAUUUXGT UTUTAUTAAAAATAUAAAAATTAAURGGGTGTGATGGRGRGTGUUTGTATTUUUAG UTAUTAGGGAGGUTGAGGUAGGAGAATUTUUTGAAUUTGGGAGGUAGGGAUTGUA GTGAGUUAAGATTGTGUUAUT 98 AGTGGUAUAATUTTGGTUAUTGUAGTUUUTGUUTUUUAGGTUAGGAGATTUTUU TGUUTUAGUUTUUUTAGTAGUTGGGAATAUAGGUARGRGUUATUAUAUURGGTTAA TTTTTGTATTTTTAGTAGAGAXGGGTTTXGUXGTGTTGGUUAGGUTGGTGTXGAAU TUUTGGGUTUAAGTGATUTGUURGUUTUAGUUTUUUAAAGTGUTGAGATTAUAGGU RGGAGUUAUTGRGUURGGUUUATAATGTGTTTAGAGTGUTUURGTGGUUAGUAUAU TAUAAAUAUAAAATGUATG 99 GGAUTGTGGGUUUUTTGGTTTGTGTUTGAAAGUTGGGGGTAUAGTTUTGUATGGGTT GGUUUUTGUUTTAUUTRGGGAAGUTUUUAGAGUUTGUTGGGUAGUUTGUUTUUTU UTUTUAUUTUUTUXGTUTUUAUTUUUTUUTUAUUAUATTURGGUTUTUUUARGGUR GGAGGUXGTGAATGGGUTGUTTTGTTGUURGGUUUAUAUAGGAGGATGGTGGUAG AAGAUUURGGUAUAAAGTUAGUAUUUAUTUTGTTUUUAGGUTGGGTTUAGGGAGG UTGAAAAGUUAUTTUAGUTGTG 100 UAUAGUTGAAGTGGUTTTTUAGUUTUUUTGAAUUUAGUUTGGGAAUAGAGTGGGTG UTGAUTTTGTGURGGGGTUTTUTGUUAUUATUUTUUTGTGTGGGURGGGUAAUAAA GUAGUUUATTUARGGUUTURGGURGTGGGAGAGURGGAATGTGGTGAGGAGGGAG TGGAGARGGAGGAGGTGAGAGGAGGAGGUAGGUTGUUUAGUAGGUTUTGGGAGUT TUURGAGGTAAGGUAGGGGUUAAUUUATGUAGAAUTGTAUUUUUAGUTTTUAGAU AUAAAUUAAGGGGUUUAUAGTUU 101 TAUTUTUTTGATGTATGAUUTTGGATGTGATTTAGUUTUTUTGGGUUTTGGUUUKUU TGAAUUATGTGATUAGAGUAUUAAGURGGUUTUUUARGUTGGTUTGAGUTGUTUAA GGGUUATUTAGGTUUTUTTTGTUUUAAGUUAGAGGTXGUUTUTUUURGGUUAAGUR GRGGUTATGGGGGTGGTGGTAUAAUAGAGAGUAUAGGGAUTTTGGAAUAUAAUAU TGGGTUATGAUUUUTGUUTGGUUAUTUTTGGUTGUTGAUUTTGAUUUTUTGTUTUU TUUTTTGTGAATGGGGGGAGT 102 AUTUUUUUUATTUAUAAAGGAGGAGAUAGAGGGTUAAGGTUAGUAGUUAAGAGTG GUUAGGUAGGGGTUATGAUUUAGTGTTGTGTTUUAAAGTUUUTGTGUTUTUTGTTG TAUUAUUAUUUUUATAGURGRGGUTTGGURGGGGAGAGGXGAUUTUTGGUTTGGG AUAAAGAGGAUUTAGATGGUUUTTGAGUAGUTUAGAUUAGRGTGGGAGGURGGUT TGGTGUTUTGATUAUATGGTTUAGRGGGGUUAAGGUUUAGAGAGGUTAAATUAUAT UUAAGGTUATAUATUAAGAGAGTA 103 GUUATGGAGAAAATATGUUATGTUTUUATGGAAAUUAAUUTATTTGUTTAAUTGAGGTTUTG GGGGTGGTTUTGAUAUTUAGTGUTAAUUAGGGGGAGTUTGGUTGTGAGGTRGTUAGUAUATG GRGGTGUTGURGGUTGUUTUUUAXGUAXGUAGGUTUTGUUAGUUTGUUTTGUUAATUTGUU AGGUAAUTGGGAUAGGTGUAGAUATGAUUUAGGUTUUAAGUAUARGUATUUAUUUTUUUR GURGAGGUAUTUTUURGGTGUUATATGTTGAUTUTGUUUAGRGUUAGGUAGUUUA 104 TGGGUTGUUTGGRGUTGGGUAGAGTUAAUATATGGUAURGGGAGAGTGUUTRGGRGGGGAG GGTGGATGRGTGTGUTTGGAGUUTGGGTUATGTUTGUAUUTGTUUUAGTTGUUTGGUAGATT GGUAAGGUAGGUTGGUAGAGUUTGXGTGXGTGGGAGGUAGURGGUAGUAURGUUATGTGUT GARGAUUTUAUAGUUAGAUTUUUUUTGGTTAGUAUTGAGTGTUAGAAUUAUUUUUAGAAUU TUAGTTAAGUAAATAGGTTGGTTTUUATGGAGAUATGGUATATTTTUTUUATGGU 105 GAGTUTGGUTGTGAGGTRGTUAGUAUATGGRGGTGUTGURGGUTGUUTUUUARGUA RGUAGGUTUTGUUAGUUTGUUTTGUUAATUTGUUAGGUAAUTGGGAUAGGTGUAG AUATGAUUUAGGUTUUAAGUAUARGUATUUAUUUTUUUXGURGAGGUAUTUTUUR GGTGUUATATGTTGAUTUTGUUUAGRGUUAGGUAGUUUAGRGUUUAUUTUUUUUT UUUUAGUUTGGUUUUARGUAUAGTGUTUTAGUUTUTGUTGGGTAGTGTGAGGAGTG GUAATUTGUAGGUAUUUTAGAAG 106 UTTUTAGGGTGUUTGUAGATTGUUAUTUUTUAUAUTAUUUAGUAGAGGUTAGAGUA UTGTGRGTGGGGUUAGGUTGGGGAGGGGGAGGTGGGRGUTGGGUTGUUTGGRGUT GGGUAGAGTUAAUATATGGUAURGGGAGAGTGUUTRGGXGGGGAGGGTGGATGRG TGTGUTTGGAGUUTGGGTUATGTUTGUAUUTGTUUUAGTTGUUTGGUAGATTGGUA AGGUAGGUTGGUAGAGUUTGRGTGRGTGGGAGGUAGURGGUAGUAURGUUATGTG UTGARGAUUTUAUAGUUAGAUTU 107 GURGAATUURGAGGGURGAGUAUUUUTUUUTUAGURGUAUTGUAUUTGUURGTAG GTGAUUAAUUUARGGGRGGAUUUUUAGAUUUAATUUTUTUUAGAGUUAGGGTGGG ATGGGUAGGGAUAGGAGURGGAGGUUUTAUTGGUUURGGGXGAAGGUATUUTGGA AAGUATUUAGAGRGTUUAGUATUUUTUURGRGGUUAUURGUAGGUTGAURGAUUU UTGGGUAGAUUUTUAGAUTUAATUUAGTUUAGGGRGGATTAAGGAGTGGGAGAUA AGGGAGURGGTGGUUURGUTGGUUU

108 GGGUUAGRGGGGUUAURGGUTUUUTTGTUTUUUAUTUUTTAATURGUUUTGGAUTG GATTGAGTUTGAGGGTUTGUUUAGGGGTRGGTUAGUUTGRGGGTGGURGRGGGAGG GATGUTGGARGUTUTGGATGUTTTUUAGGATGUUTTXGUURGGGGUUAGTAGGGUU TURGGUTUUTGTUUUTGUUUATUUUAUUUTGGUTUTGGAGAGGATTGGGTUTGGGG GTURGUURGTGGGTTGGTUAUUTARGGGUAGGTGUAGTGRGGUTGAGGGAGGGGTG UTRGGUUUTRGGGATTRGGU 109 TTGUTTGAUUAAAAGAATGUAGUAGAUATAAUTTTGAGAUUTGGAGUTAGGTUAUA AGARGATTTUUTGGGTTTTGTGGAATTUTRGTTUTGAAAGAAAUAAGUUAUUAAGT GGURGGGTGAGUTGGUTUAXGUUTGTAATUUUAGUAUTTTGGGAGGUXGAGURGG GUXGATUAUAAGGTUAGGAGATRGAGAUUATUUTGGUTAAUATGGTGAAAUUURG TUTUTAUTAAAAATAUAAAAAAATTAGURGGGUATAUTGGRGGGRGUUTGTAGTUU UAGUTAUTRGGGAGGUTGAGGU 110 GUUTUAGUUTUURGAGTAGUTGGGAUTAUAGGRGUURGUUAGTATGUURGGUTAAT TTTTTTGTATTTTTAGTAGAGARGGGGTTTUAUUATGTTAGUUAGGATGGTUTRGATU TUUTGAUUTTGTGATXGGUURGGUTXGGUUTUUUAAAGTGUTGGGATTAUAGGXGT GAGUUAGUTUAUURGGUUAUTTGGTGGUTTGTTTUTTTUAGAARGAGAATTUUAUA AAAUUUAGGAAATRGTUTTGTGAUUTAGUTUUAGGTUTUAAAGTTATGTUTGUTGU ATTUTTTTGGTUAAGUAA 111 AGAATUTGUUTAGUAGGRGGUTUTUUUUTGUTUUUUUAURGAGUAUAUAUKUIUU GAGGGGAUUUTGRGGGAGGAGGUTGUTTUAGTUTUUAGAGAUUATUTUUUATUTUT AUAGRGAUTUUUUTATGAURGTUUUUUAUURGGTGUTUTXGGGUUARGGGGAAGG GAUAUTRGGGAAAGAUAUUAGAGAURGGGAGGGTGUAGUTGGGUTUTTRGRGGGG AGRGGGRGGGAGGUUTTUUTGTTAUATGTRGUAGUTGGGAUAUAGARGGUAGRGUT UUAGGGTUUAUTTGURGGUTTRG 112 RGAAGURGGUAAGTGGAUUUTGGAGRGUTGURGTUTGTGTUUUAGUTGRGAUATGT AAUAGGAAGGUUTUURGUURGUTUUURGRGAAGAGUUUAGUTGUAUUUTUURGGT UTUTGGTGTUTTTUURGAGTGTUUUTTUUURGTGGUUXGAGAGUAURGGGTGGGGG ARGGTUATAGGGGAGTRGUTGTAGAGATGGGAGATGGTUTUTGGAGAUTGAAGUAG UUTUUTUURGUAGGGTUUUUTUUUARGGTUTGTGUTRGGTGGGGGAGUAGGGGAG AGURGUUTGUTAGGUAGATTUT 113 AGGUUUAGGUAGAGGTUAGAGUUUAAGUUUTGTUUURGAAGGAAATGTGTUUUAT GUTAAUTAUTUUATAGUTGAGGUUTGGAGGGAAGTUAGGGAUUUTGGGAUTGGTTA TUUTGGUUTTGAUTUATTAUTGTTURGGAGAUUTAAAXGUAUUUTGAGUUAUUAGA XGTGGGTGTTAAUAUUTGAGGTUAAUUUUUTGAXGUTTURGGUTGUTUTGGAGGAA GUTGGTUUTUUUTUUUAUUTUUTGTTTTURGTGUUAGUUTGGTAUAGAGTUAAGGG GUTTGGUTGGGUTTGGUTGGG 114 UUAGUUAAGUUUAGUUAAGUUUUTTGAUTUTGTAUUAGGUTGGUARGGAAAAUAG GAGGTGGGAGGGAGGAUUAGUTTUUTUUAGAGUAGURGGAAGXGTUAGGGGGTTG AUUTUAGGTGTTAAUAUUUAXGTUTGGTGGUTUAGGGTGXGTTTAGGTUTURGGAA UAGTAATGAGTUAAGGUUAGGATAAUUAGTUUUAGGGTUUUTGAUTTUUUTUUAG GUUTUAGUTATGGAGTAGTTAGUATGGGAUAUATTTUUTTRGGGGAUAGGGUTTGG GUTUTGAUUTUTGUUTGGGUUTG 115 UUUATGUTAAUTAUTUUATAGUTGAGGUUTGGAGGGAAGTUAGGGAUUUTGGGAU TGGTTATUUTGGUUTTGAUTUATTAUTGTTURGGAGAUUTAAAXGUAUUUTGAGUU AUUAGAXGTGGGTGTTAAUAUUTGAGGTUAAUUUUUTGAXGUTTURGGUTGUTUTG GAGGAAGUTGGTUUTUUUTUUUAUUTUUTGTTTTURGTGUUAGUUTGGTAUAGAGT UAAGGGGUTTGGUTGGGUTTGGUTGGGUTUAGAAARGTGGUAGTUAGGAGUUAGU UTGRGGGUAGRGGGGTGUTGGG 116 UUUAGUAUUURGUTGUURGUAGGUTGGUTUUTUAUTGUUARGTTTUTGAGUUUAG UUAAGUUUAGUUAAGUUUUTTGAUTUTGTAUUAGGUTGGUARGGAAAAUAGGAGG TGGGAGGGAGGAUUAGUTTUUTUUAGAGUAGURGGAAGXGTUAGGGGGTTGAUUT UAGGTGTTAAUAUUUAXGTUTGGTGGUTUAGGGTGXGTTTAGGTUTURGGAAUAGT AATGAGTUAAGGUUAGGATAAUUAGTUUUAGGGTUUUTGAUTTUUUTUUAGGUUT UAGUTATGGAGTAGTTAGUATGGG 117 UTUTUUURGUAGTTTUATURGTUUTUUTUUURGUUTUTGRGAGUTGGGTTTGGGGAR GTUTGGGTGGAATGTAGAUUUAUAGGUTGTUUTTGGTGUUUTUUUTUUUTGTTUTU UAGRGUUUUAGUUUUAGAUAUUAGTUUUUUAGRGGGXGAAAGUURGGGAGRGUU TTUUURGAAAGAUATUAGGGTGUUARGRGGUUUUTGUUUTGUAGAAGUATUUUUU TUURGUUUUTGUUTGGAAAGUAGGUUUUTUUUTAAGUTUTGRGUUUTTUTTUUUTG GGRGUUUTRGGAURGTGGUURG 118 RGGGUUARGGTURGAGGGRGUUUAGGGAAGAAGGGRGUAGAGUTTAGGGAGGGGU UTGUTTTUUAGGUAGGGGRGGGAGGGGGATGUTTUTGUAGGGUAGGGGURGRGTG GUAUUUTGATGTUTTTRGGGGAAGGRGUTUURGGGUTTTXGUURGUTGGGGGAUTG GTGTUTGGGGUTGGGGRGUTGGAGAAUAGGGAGGAAGGGUAUUAAGGAUAGUUTG TGGGTUTAUATTUUAUUUAGARGTUUUUAAAUUUAGUTRGUAGAGGRGGGGAGGA GGARGGATGAAAUTGRGGGGAGAG 119 AGAGGAGTGGGGAGRGUAGUAGGGTGGUUUURGUTUURGUTUAGAGGAGUTGGUU UTTTAAGGUUAGGUUUAGGRGGGTRGGGAAUAGAGAUURGGGAATGTGGGUTGGA UTGGGGAGUAGAGUUAUUUAGUATGAGTUATTUURGTTTXGURGGAUTUTTRGURG UTGGUTUTRGUTTGURGUUUTUUUUTGGUUUTGGUUUTGGUUTUTGRGUUUTUUUT GUAGAGUTGGTURGGGTGGGUTGGRGGUUTUUAUURGUUAUAAGRGUAUAGGGUT UTGUUUAUTUUURGUUUUTTTTU 120 GAAAAGGGGRGGGGAGTGGGUAGAGUUUTGTGRGUTTGTGGRGGGTGGAGGURGU UAGUUUAUURGGAUUAGUTUTGUAGGGAGGGRGUAGAGGUUAGGGUUAGGGUUA GGGGAGGGRGGUAAGRGAGAGUUAGRGGRGAAGAGTURGGXGAAARGGGAATGAU TUATGUTGGGTGGUTUTGUTUUUUAGTUUAGUUUAUATTUURGGGTUTUTGTTUUR GAUURGUUTGGGUUTGGUUTTAAAGGGUUAGUTUUTUTGAGRGGGAGRGGGGGUU AUUUTGUTGRGUTUUUUAUTUUTUT 121 GURGAGRGRGGTGGUTUATGUUTGTAATUUUAGUAUTTTGGGAGARGGAGGTGGGT GGATUAUUTUAGGTUAGAAGTTTGAGAUUTUTGTUTUTAUTGAAAUTATAAAAAAT TGGURGGGUATGGTGGTGGGTGTUTGTAGTTUUAGUTAXGTGGTAAGUTGAGGUAG GAGAATGAUTTGAAUURGGGAGGRGGAGGTTGUAGTGAGUUAGGATTGRGUUAUT GUAUTUUAGUUTGGGAGAUAGAGTUAGAUTUTGTUTUAAAAAAAAGUTATGGGUU TGUAGGATGUUTAATATAAAAG 122 UTTTTATATTAGGUATUUTGUAGGUUUATAGUTTTTTTTTGAGAUAGAGTUTGAUTU TGTUTUUUAGGUTGGAGTGUAGTGGRGUAATUUTGGUTUAUTGUAAUUTURGUUTU URGGGTTUAAGTUATTUTUUTGUUTUAGUTTAUUAXGTAGUTGGAAUTAUAGAUAU UUAUUAUUATGUURGGUUAATTTTTTATAGTTTUAGTAGAGAUAGAGGTUTUAAAU TTUTGAUUTGAGGTGATUUAUUUAUUTURGTUTUUUAAAGTGUTGGGATTAUAGGU ATGAGUUAURGRGUTRGGU 123 UARGUTUUTGTTTUAUTTTUATGTTUTGUTUTGTAUAUUTGGUTURGUUTTUTAGAT AGUAATAGUAGAATTAGTGAAAGTATTAAAGTUTTTGATUTTTUTGAGAAGAGUAT AGAAGAAATAATGARGTAAGUTGTUUTUTUTUUAGUTXGGUTAUUTAAAAGGGAAA GGUUUUUTGTURGGTGGAUARGTGAUTUAUATGAUUTTATTAATUAUTGGAGATGA UTUAUAUTUUTTAUUUTGUUUUTTTGUUTTGTAUAUAATAAATAAUAGRGRGAUUA GGUATTRGGGGUUAUTGUU 124 GGUAGTGGUUURGAATGUUTGGTRGRGUTGTTATTTATTGTGTAUAAGGUAAAGGG GUAGGGTAAGGAGTGTGAGTUATUTUUAGTGATTAATAAGGTUATGTGAGTUARGT GTUUAURGGAUAGGGGGUUTTTUUUTTTTAGGTAGUXGAGUTGGAGAGAGGAUAG UTTARGTUATTATTTUTTUTATGUTUTTUTUAGAAAGATUAAAGAUTTTAATAUTTTU AUTAATTUTGUTATTGUTATUTAGAAGGRGGAGUUAGGTGTAUAGAGUAGAAUATG AAAGTGAAAUAGGAGRGTG 125 AGUUUUUTGGGRGGGGTURGGGGAGUAGGUURGUATTTGGAGGAUAGGGTGTGAU UUATUTGAATUUTRGTTAAAGTAAAAGURGAURGARGGUTUTGGGAGGTTTGAGGU UTGGRGGGGRGGUUURGGGAAGTGATTTGTGGUXGUTAGGXGRGXGUTGGAAAUU UTTTUUUATUTGRGGAGUUUAURGGAGUTGTGATRGGAGGAGGAATTUUUUUAGGU AGGGAGGAURGUAGGGUUTTTTTUAUTRGTUUTGAGGGGUUUTGGGGUTTGGGGAG UAAAUUTGGGGTGAUUUATTTU 126 GAAATGGGTUAUUUUAGGTTTGUTUUUUAAGUUUUAGGGUUUUTUAGGARGAGTG AAAAAGGUUUTGRGGTUUTUUUTGUUGGGGGAATTUUTUUTURGATUAUAGUTUR GGTGGGUTURGUAGATGGGAAAGGGTTTUUAGXGRGXGUUTAGXGGUUAUAAATU AUTTUURGGGGURGUUURGUUAGGUUTUAAAUUTUUUAGAGURGTRGGTRGGUTTT TAUTTTAARGAGGATTUAGATGGGTUAUAUUUTGTUUTUUAAATGRGGGUUTGUTU UURGGAUUURGUUUAGGGGGUT 127 UATUUAUAAAUUTUUUAGGUUUUUTUAUTUTTUURGUAUAGTUTGUUTURGGTGUT UUAGAAAGAUTGGAAATGAGGTGAGUTUUUTTGGATUUUTGUUTGUUAUUTGUAA ATATUATGTGGTGUTAUTTGUUUTUUTGTUUUTUUTUUXGTUUUAGGUUAATUUTU UUAUUUUUTTAATTGUURGGGGATUTUUATTAUTTAAAUUTTTUUAUTGGTAUUTUT UUTUUUAUAUAAGUUTUUTUAGUTGTTTTURGTUTTTAAUUAAUAUUTTUUUTGGU TUUAGUTAUTGUUAUTTUAT 128 ATGAAGTGGUAGTAGUTGGAGUUAGGGAAGGTGTTGGTTAAAGARGGAAAAUAGU TGAGGAGGUTTGTGTGGGAGGAGAGGTAUUAGTGGAAAGGTTTAAGTAATGGAGAT UUURGGGUAATTAAGGGGGTGGGAGGATTGGUUTGGGAXGGGAGGAGGGAUAGGA GGGUAAGTAGUAUUAUATGATATTTGUAGGTGGUAGGUAGGGATUUAAGGGAGUT UAUUTUATTTUUAGTUTTTUTGGAGUAURGGAGGUAGAUTGTGRGGGAAGAGTGAG GGGGUUTGGGAGGTTTGTGGATG 129 UTTTUUUAGGAUTGUUTTGGUUUUUTGGUUUUAGTUTGGAGGAUTUTTGUTUAUTT UUTURGUUUUUAGGTGAGUTGAGAAUUUAUTGRGRGRGGGAUTUTGUTGRGUUTG UUUTUURGGGUTGUAGAGGGUAGGAXGUAURGUUAGGUAAGGURGRGGUTUTGXG UTGATGUUAUTURGGGAGRGGGTGGUTGRGGGGGAGGAGGGRGAGUAUTGGARGG GGGUAGRGGAGTGTAGGGTGTGAGATUTAAAUAGAGGGUTUUAUTGGAGGGUTTG UUUAGAAGGRGGUAGTUAUAUTGG 130 UUAGTGTGAUTGURGUUTTUTGGGUAAGUUUTUUAGTGGAGUUUTUTGTTTAGATU TUAUAUUUTAUAUTURGUTGUUUURGTUUAGTGUTRGUUUTUUTUUUURGUAGUUA UURGUTUURGGAGTGGUATUAGXGUAGAGURGRGGUUTTGUUTGGRGGTGXGTUUT GUUUTUTGUAGUURGGGAGGGUAGGRGUAGUAGAGTUURGRGRGUAGTGGGTTUT UAGUTUAUUTGGGGGRGGAGGAAGTGAGUAAGAGTUUTUUAGAUTGGGGUUAGGG GGUUAAGGUAGTUUTGGGAAAG 131 TTTAGGGTUTUTUTUURGUUTUTTTTUUTUUUURGUTUUUTUTUTUUTTGRGGUTGA UTUUAGUTUUUUUTRGGTGUURGTAAUUUTUUTTTUUTUTTTTGUXGUAGTUTUXG TUTUTUTTUUAUAGGGTUTUTUUUTUUUUUTUTUUURGTGGTTGTUAGAUTTTUTUU TGGAUTTTUTURGUUURGUAURGUUXGUUURGGATGURGAGRGTGGTAGAUTUTGU AGURGGGUTUUTRGUTGUURGUTGGRGUTGUUTAUAUUUUUTTGGGUTUUUUTUUA AGGTUUUUTURGUTRGU 132 GRGAGRGGAGGGGAUUTTGGAGGGGAGUUUAAGGGGGTGTAGGUAGRGUUAGRGG GUAGRGAGGAGUURGGUTGUAGAGTUTAUUARGUTRGGUATURGGGGXGGGRGGT GRGGGGRGGAGAAAGTUUAGGAGAAAGTUTGAUAAUUARGGGGAGAGGGGGAGGG AGAGAUUUTGTGGAAGAGAGAXGGAGAUTGXGGUAAAAAGAGGAAAGGAGGGTTA RGGGUAURGAGGGGGAGUTGGAGTUAGURGUAAGGAGAGAGGGAGRGGGGGAGG AAAAGAGGRGGGAGAGAGAUUUTAAA 133 GAGGGUUAUAGTAAAUTGGAUAAGTTTTTUTGUUUAGUUTAGGUTGUUAUUTGTAG GTUAUTTGGGUTUUAGUTATGTGGUTGUUTUTTUTGUTGGGTGUUTTAUTUTGGGUA GTGUTGTGGTTGUTUAGGGAURGGUAGAGUUTGUUXGUUAGUAATGUUTTTGTUTT UATUAURGGUTGTGAUTUAGGUTTTGGGRGUUTTUTGGUAUTGUAGUTGGAUUAGA GAGGUTTURGAGTUUTGGUUAGUTGUUTGAUUUUUTURGGGGURGAGGAUUTGUA GRGGGTGGUUTUUTUURGUU 134 GRGGGAGGAGGUUAUURGUTGUAGGTUUTRGGUUURGGAGGGGGTUAGGUAGUTG GUUAGGAUTRGGAAGUUTUTUTGGTUUAGUTGUAGTGUUAGAAGGRGUUUAAAGU UTGAGTUAUAGURGGTGATGAAGAUAAAGGUATTGUTGGXGGGUAGGUTUTGURG GTUUUTGAGUAAUUAUAGUAUTGUUUAGAGTAAGGUAUUUAGUAGAAGAGGUAG UUAUATAGUTGGAGUUUAAGTGAUUTAUAGGTGGUAGUUTAGGUTGGGUAGAAAA AUTTGTUUAGTTTAUTGTGGUUUTUA 135 GTTUTGGUTTUATTTTTTTTTTUUUAAAATGUUATTTTUATTTGTTUTTAGAGTTUAG AAUATGTUAAAGAGUTTUTTTAAGUAGTAGGTGGTTTTAUAGAGUUUAUAGAGAAG GAAAAUTAAATATUATUURGGATGUAGTUUAUTAXGATXGTGGAGGAGTUAGATTA UTUTURGGGUTTTGUTGTGTUTGUTTGTGAAAUAGGAAAGGGAGAAUTGAGGUAAT GAGTUAUUTUAUTTGGGUUUAAAGUAUUAUUTARGTTGAATATGGAGAAAATGTGA AGUAAGAGTTTUTTTTTA 136 TAAAAAGAAAUTUTTGUTTUAUATTTTUTUUATATTUAARGTAGGTGGTGUTTTGGG UUUAAGTGAGGTGAUTUATTGUUTUAGTTUTUUUTTTUUTGTTTUAUAAGUAGAUA UAGUAAAGUURGGAGAGTAATUTGAUTUUTUUAXGATXGTAGTGGAUTGUATURGG GATGATATTTAGTTTTUUTTUTUTGTGGGUTUTGTAAAAUUAUUTAUTGUTTAAAGA AGUTUTTTGAUATGTTUTGAAUTUTAAGAAUAAATGAAAATGGUATTTTGGGAAAA AAAAAATGAAGUUAGAAU 137 UUTUUTUUAGTUTTTGUATATATAUUAGGUTGGTATUUATTGUAGGTGGGGAUUTU UTUTTTGGGUTTTGGAGUUUUUUTUUUTGTGTUTUTGTAURGGGGAGUTTUTTUUTT UTGTUTTUTUUUTTUUTTUTTGUTUATTAAAUTUTUXGUTUUTTAAAAUUAUTUUAR GTGTGTURGTGTTGTTTTATUTAAAURGGRGGUAGGATUAAGAAUUUTTGTGT GUAUTUATUAGAGURGTATGATAATUAAGAGUTGAUTAUUTGGGUUATTUTUATAU UATTAGTGURGUATTTA 138 TAAATGRGGUAUTAATGGTATGAGAATGGUUUAGGTAGTUAGUTUTTGATTATUAT ARGGUTUTGATGAGTGUAGGAAUAUAAGGGTTUTTGATUUTGURGURGGTTTAGAT AAAAUAAUARGGAUAUARGTGGAGTGGTTTTAAGGAGXGGAGAGTTTAATGAGUAA GAAGGAAGGGAGAAGAUAGAAGGAAGAAGUTUUURGGTAUAGAGAUAUAGGGAG GGGGGUTUUAAAGUUUAAAGAGGAGGTUUUUAUUTGUAATGGATAUUAGUUTGGT ATATATGUAAAGAUTGGAGGAGG 139 AAGGTTAAAGTRGUTGUTAGAUUAAGGUTAAAURGTGGRGAGGTAGTTGUTTGRGU RGUAGAGTGTGGGTGTGAAUAGUTGGAGUTUAGTGGTTUUTGGAGAUTUAGGGAUU AUUTGTATTUUAUATURGGUTTUUUAUUUARGUAUAXGUAGTATGAUUTGGGTTTU UUUTTTATAUAGTGGAATGUTAAGTGUUTAUAUUUTAGURGGGGTUAGUUAAUTAT GGUUTGTGGGUAUUATUUUAUUTGUAGUUTGTTTTTGAGUTAAGAATGTTGTTGAU AUTTITAAAAAUAGAGAAUA 140 GTTUTUTGTTTTTAAAAGTGTUAAUAAUATTUTTAGUTUAAAAAUAGGUTGUAGGTG GGATGGTGUUUAUAGGUUATAGTTGGUTGAUUURGGUTAGGGTGTAGGUAUTTAGU ATTUUAUTGTATAAAGGGGAAAUUUAGGTUATAUTGXGTGTGRGTGGGTGGGAAGU RGGATGTGGAATAUAGGTGGTUUUTGAGTUTUUAGGAAUUAUTGAGUTUUAGUTGT TUAUAUUUAUAUTUTGRGGRGUAAGUAAUUTAUUTRGUUARGGTTTAGUUTTGGTUT AGUAGRGAUTTTAAUUTTG 141 GAGAUAGGGTTTUAUTUUTGTRGUUUAGGUTGGAGTGUAGUUTUAAUUTUUTGGGU TUAGTGGATUTTUUUAUUTUAGAUTUUTGAGTAGURGGGAUTAUAGGUAUARGUUA UUAGGUUTAGUTAATTTTTTGTATTTTTTTGTAGAGAXGAGGTTTRGUTAGGTrGUU UAGGUTGGTUTUTAAUTUUTGGGUTUAAGXGATUUAUUUAUUTUAGUTTUUUAAAG TGUTGGGGTTAUAGGUUTGAGTUAUAGXGTURGGUTGAAAGTGAAGTTGAATGAGA TGAUTRGTUUAGGUUAUAT 142 ATGTGGUUTGGARGAGTUATUTUATTUAAUTTUAUTTTUAGURGGAXGUTGTGAUT UAGGUUTGTAAUUUUAGUAUTTTGGGAAGUTGAGGTGGGTGGATXGUTTGAGUUUA GGAGTTAGAGAUUAGUUTGGGUAAUUTAGRGAAAUUTXGTUTUTAUAAAAAAATA UAAAAAATTAGUTAGGUUTGGTGGRGTGTGUUTGTAGTUURGGUTAUTUAGGAGTU TGAGGTGGGAAGATUUAUTGAGUUUAGGAGGTTGAGGUTGUAUTUUAGUUTGGGR GAUAGGAGTGAAAUUUTGTUTU 143 AUARGUUAUUAGGUUTAGUTAATTTTTTGTATTTTTTTGTAGAGAXGAGGTTTRGOT AGGTTGUUUAGGUTGGTUTUTAAUTUUTGGGUTUAAGXGATUUAUUUAUUTUAGUT TUUUAAAGTGUTGGGGTTAUAGGUUTGAGTUAUAGXGTURGGUTGAAAGTGAAGTT GAATGAGATGAUTRGTUUAGGUUAUATGGUAATUAGTGGUTGATTGARGUUAAAGT TGATTTUATTUTTUTUAATGGGTTUAGAGTUUAAATTUTGGAAUUTUAGAAGARGTT GUTATTUTGGTTUUAAGU

144 UTTGGAAUUAGAATAGUAARGTUTTUTGAGGTTUUAGAATTTGGAUTUTGAAUUUA TTGAGAAGAATGAAATUAAUTTTGGRGTUAATUAGUUAUTGATTGUUATGTGGUUT GGARGAGTUATUTUATTUAAUTTUAUTTTUAGURGGAXGUTGTGAUTUAGGUUTGT AAUUUUAGUAUTTTGGGAAGUTGAGGTGGGTGGATXGUTTGAGUUUAGGAGTTAGA GAUUAGUUTGGGUAAUUTAGRGAAAUUTXGTUTUTAUAAAAAAATAUAAAAAATT AGUTAGGUUTGGTGGRGTGTG 145 AGTGAUTGUAGRGTUAGGUUAAGUTTGGUUAUTTAUATGTUTGGUATGAUAGTGGU UTUAGAGTAUTRGTUTGAGAAGAAGAGUTATUAUUTGAGRGUTUTGGAGAAUTTAG URGGAGUTTTUAGGUAGTUTGGGAGUUTAUATGGAGGXGTGTAGGUTTATGTUTUA TGTUUARGTTGUURGGGAGAUAAAATUUTTTUTTTATTTAGAGUTGUUUUAAAATG UTGUAUUAGUTTUTUAUTGRGGTGGUTTUAUUTTAGUATAUAGGTATGTGGARGGU UAUTGTGUTGGUTUAUUTT 146 AAGGTGAGUUAGUAUAGTGGURGTUUAUATAUUTGTATGUTAAGGTGAAGUUAUR GUAGTGAGAAGUTGGTGUAGAAUATTTTGGGGUAGUTUTAAATAGAAAAGGATTTT GTUTUURGGGUAARGTGGAUATGAGAUATAAGUUTAUAXGUUTUUATGTAGGUTUU UAGAUTGUUTGAAAGUTURGGUTAAGTTUTUUAGAGRGUTUAGGTGATAGUTUTTU TTUTUAGARGAGTAUTUTGAGGUUAUTGTUATGUUAGAUATGTAAGTGGUUAAGUT TGGUUTGARGUTGUAGTUAUT 147 RGGGUAUUTAGGTUTRGUURGUUTGUAGURGUUTGGGGARGRGGGTTURGGARGGU TGGRGRGGGGRGGGGRGGGGAUUAURGAGUAGGAAGTUUURGRGGAAGRGURGUR GGGUAUAGRGTGGGTGUTGTRGAGGAGTGGRGUURGGGXGGGGRGGGAGGTTATA AATAGRGGURGUUATUUTGUTTUTUTTUAGAUAUAUTTAATTTAGURGGUAGGUAU ARGGATGUTTATTTTTAAAAAAAGAAUTTGTTTTATTGRGUTRGAGGTGAURGGGAA GGTGTUUURGRGGGTUAUTRG 148 RGAGTGAUURGRGGGGAUAUUTTUURGGTUAUUTRGAGRGUAATAAAAUAAGTTUT TTTTTTAAAAATAAGUATURGTGTGUUTGURGGUTAAATTAAGTGTGTUTGAAGAGA AGUAGGATGGRGGURGUTATTTATAAUUTUURGUTGUURGGGRGUUAUTUUTRG AUAGUAUUUARGUTGTGUURGGRGGRGUTTURGRGGGGAUTTUUTGUTRGGTGGTU UURGUUURGUUURGRGUUAGURGTURGGAAUURGRGTUUUUAGGRGGUTGUAGGR 149 GGGRGAGAUUTAGGTGUURG GAAGGTGRGGTGRGGTGAGGTGAGAAGAGAGAURGRGUTAGAUUAGGRGATGTUTT AGGGARGGGAGAGGGGTGAGGUUUARGGRGGTUUTGGGGAGRGGUUUARGAURGG UUUARGUAGAGUTTGTAGUUAGTGAAUAGGAAGTATTGGXGAGAGGGAUTGAGAA AUUUAAGAGAGTGTGGGGTGAGGAAAAGGTUAAGGAAGGUUUAGGUTTUUAGGAA GGGUUTGGGURGGGGRGGGGRGGGTGGTGGGAGGUAGTGGTTAGGARGGGRGGGG GTGGGGGTGGGGGTGGGGGTAGGG 150 UUUTAUUUUUAUUUUUAUUUUUAUUUURGUURGTUUTAAUUAUTGUUTUUUAUUA UURGUUURGUUURGGUUUAGGUUUTTUUTGGAAGUUTGGGUUTTUUTTGAUUTTTT UUTUAUUUUAUAUTUTUTTGGGTTTUTUAGTUUUTUTXGUUAATAUTTUUTGTTUAU TGGUTAUAAGUTUTGRGTGGGURGGTRGTGGGURGUTUUUUAGGAURGURGTGGGU UTUAUUUUTUTUURGTUUUTAAGAUATRGUUTGGTUTAGRGRGGTUTUTUTTUTUA TTTTTTTATTRUATURGUAUUTTU 151 GAGAAAUAAAATAUATTTTTTAATTTAAAAAAAAGTAUUAGAATGAATAAAAUAGG GGUTTTUUAAAAUTGUTTTTGGTAGATTTAGUAAAUUTAUTGAAUTTTAGAAAUTTTU ATTTTATAATTGTURGGAGATAGAAAGUAGTGUTTUXGAATAAGTGGATAAUTUTGU RGGTUUUAGTAGGTGUUATTGGTGAGUAUAUAGGGTTGUTTAAGTUTUTAAGTUAT TTUUUTGAUTGTGGTTTGAATUAATGTUAAATATUTAUAGGGGTUAGGUAGGTAAU TUAATGAAGTGAAAUAGG 152 UTGTUAUTTUATTGAGTTAUUTGUUTGAUUUUTGTAGATATTTGAUATTGATTUA AAUUAUAGTUAGGGAAATGAUTTAGAGAUTTAAGUAAUUUTGTGTGUTUAUUAATG GUAUUTAUTGGGAURGGUAGAGTTATUUAUTTATTXGGAAGUAUTGUTTTUTATUT URGGAUAATTATAAAATGAAAGTTTUTAAGTTUAGTAGGTTTGUTAAATUTAUUAAA AGUAGTTTTGGAAAGUUUUTGTTTTATTUATTUTGGTAUTTTTTTTTAAAUUAAAAAA TGTATTTTGTTTUTUT 153 GGAGGGUTTUAURGTUAGRGTAGRGTARGUUTGRGGGURGGGGRGGGAGAGGGAU RGTRGRGTTTGTGURGUUAGUAUUTGRGGUUUUUAGRGUAUURGGGUUUUARGRG GTAGUUUUUAGGGAGTGGGGAGTRGGGRGGGAAAUAGUTXGUURGGGUTUUTARG GGTGUUUUTTTRGURGRGUTUUUTUURGAGGGTUUTTTGUAGTRGGGRGTGGAAGT GGGATGAGUAAAUUURGUAGUAUAGGGUUTTRGUUUUAGGAUUTGUAUUUTUTAU RGGUUARGGGARGTUUUTURGUAU 154 GTGRGGAGGGARGTUURGTGGURGGTAGAGGGTGUAGGTUUTGGGGRGAAGGUUU TGTGUTGRGGGGTTTGUTUATUUUAUTTUUARGUURGAUTGUAAAGGAUUUTRGGG AGGGAGRGRGGRGAAAGGGGUAUURGTAGGAGUURGGGXGAGUTGTTTUURGUUR GAUTUUUUAUTUUUTGGGGGUTAURGRGTGGGGUURGGGTGRGUTGGGGGURGUA GGTGUTGGRGGUAUAAARGRGARGGTUUUTUTUURGUUURGGUURGUAGGRGTAR GUTARGUTGARGGTGAAGUUUTUU 155 AGAUAUAAAGAGGGRGGAGAGAUAGAUAUAGAAAGAGGGAGAUAGRGGGGUTGG ATGGARGTGTGGURGGGUUAGTGGGGAGGAGAGARGAGTURGUAGAUAGRGTTUA GAGGURGRGUTGUTTTGGGTGUTGAGURGTUURGGGGTTUAXGGTRGUAGTTTGTUU TTAUAAAARGUUUAGURGUUURGAUUTGTGGTGUTTAGGGAGGAUUTAUUTGGUTG TGURGGTUTGAGAAGGGGUUAGTGAGGUURGGTGRGGGTARGGGRGGGTGUAGAT GUAGUUAGGAGGARGGGRGGGAGU 156 GUTUURGUURGTUUTUUTGGUTGUATUTGUAUURGUURGTAUURGUAURGGGUUTU AUTGGUUUUTTUTUAGAURGGUAUAGUUAGGTAGGTUUTUUUTAAGUAUUAUAGG TRGGGGRGGUTGGGRGTTTTGTAAGGAUAAAUTGRGAUXGTGAAUUURGGGARGGU TUAGUAUUUAGGUAGRGRGGUUTUTGAARGUTGTUTGRGGAUTRGTUTUTUUTUUU UAUTGGUURGGUUAUARGTUUATUUAGUUIRGUTGTUTUUUTUTITUTGTGTUTGT UTUTURGUUUTUTTTGTGTUT 157 GUTGTUAUAUTGAGUTGTTTAAUAUTTAAGATGTTGGTGGATGGUAAAGUTAAAAG AGUATUGTAAUAUATGAUUTUTGGGGUTUURGGAGTUATGAGTAUUUUTTUTAGAU AUAGURGTGGGGUUAUAUAGAATTUTGUTUUTGUTGUXGUURGGAAGUAUTUATUT GGUTUUTGUAUUUAUTUAUUTGUATUUTTUUUUTUUUARGAGGTGTTAAGAGUTGT GGGATGAGTAAAGGAGGUUTGTGAAGGATTTUUTGTTTUAGTUTTAUATTUAGGTUT GAGTTUTUAGAGGAATUTT 158 AAGATTUUTUTGAGAAUTUAGAUUTGAATGTAAGAUTGAAAUAGGAAATUUTTUAU AGGUUTUUTTTAUTUATUUUAUAGUTUTTAAUAUUTRGTGGGAGGGGGAGGATGUA GGTGAGTGGGTGUAGGAGUUAGATGAGTGUTTURGGGXGGUAGUAGGAGUAGAAT TUTGTGTGGUUUUARGGUTGTGTUTAGAAGGGGTAUTUATGAUTURGGGAGUUUUA GAGGTUATGTGTTAUAGTGUUUTTTAGUTTTGUUATUUAUUAAUATUTTAAGTGTT AAAUAGUTUAGTGTGAUAGU 159 UAGGGUTGGGAGAATAGGATGGAUAGRGTTTTGUUAGAGUUTUATGGGAAGUTTUU TTTUAGGUAGUTGAAUUUATTTUAGGGGTAGGGAGUAUTGATUAGGGGTTGGGAUA TTGUUURGGGAGGAGGATGAGGATGTTTUUAGGUUTXGGUTGAUTUATGGTAGTGA GTATTAGTUAUTUUUTUAUAAGAATUAGUUUAUATUUTUTAGTAGUUTUTTGTUTU UUAGAGGUUUUTGUUUUATGTTTAUUTGUUTGAAGUTUUTUTUURGGURGUUUUUA UUUAUATURGUAUAGTTTGG 160 UAAAUTGTGRGGATGTGGGTGGGGGRGGURGGGAGAGGAGUTTUAGGUAGGTAAA UATGGGGUAGGGGUUTUTGGGAGAUAAGAGGUTAUTAGAGGATGTGGGUTGATTUT TGTGAGGGAGTGAUTAATAUTUAUTAUUATGAGTUAGUXGAGGUUTGGAAAUATUU TUATUUTUUTUURGGGGUAATGTUUUAAUUUUTGATUAGTGUTUUUTAUUUUTGAA ATGGGTTUAGUTGUUTGAAAGGAAGUTTUUUATGAGGUTUTGGUAAAARGUTGTUU ATUUTATTUTUUUAGUUUTGU 161 GAGGAUTAAAAGAAGUUAGAGATGUTGGTUAATTGAUAUAAAAATAAAGAGUTAA GGGAGAGGTTGAGAGAGGGAGAGUAATATUTATGGGTGTUTGGAATTTTTAAAGGG UTUAGAGGAGGAGGGGGURGGGRGTGGTGGUTUAXGUUTGTTATUXGAGUAUTTTG GGAGGUUAAGGTGGGUAAATUARGAGGTUAGGAGTTTGAGAGUAGUUTGAUUAAU ATGGTGUAAUUURGTUTUTAUTAAAAATAUAAAATTTAGURGGGTGTGGTTGTGTG UUTGTAATUUUAGUTAUTUAGG 162 UUTGAGTAGUTGGGATTAUAGGUAUAUAAUUAUAUURGGUTAAATTTTGTATTTTT AGTAGAGARGGGGTTGUAUUATGTTGGTUAGGUTGUTUTUAAAUTUUTGAUUTRGT GATTTGUUUAUUTTGGUUTUUUAAAGTGUTXGGATAAUAGGXGTGAGUUAUUARG UURGGUUUUUTUUTUUTUTGAGUUUTTTAAAAATTUUAGAUAUUUATAGATATTGU TUTUUUTUTUTUAAUUTUTUUUTTAGUTUTTTATTTTTGTGTUAATTGAUUAGUATUT UTGGUTTUTTTTAGTUUTU 163 UUAGGAGUURGUUTGGGAGRGRGUAGRGUTUTAGGAGURGAGAGURGUTGUTTGG UUUTRGUTGGURGGGTAAAURGAGGGGAAGUTUUTGGUUTUUTTTUUUTTAAGUUU UTTATTGUTTUTGTGGGGAAGGUUUTUUTAGGTAGAGGXGAAGGAURGGGGAGATA AUUTUTUUUATGGGUUAUATURGUTGUUATGGTUTGTGTRGTGUUAGAAGGTAUUT UTUAGUUUTUAGTGURGTGAAAAATUTGAUAUTUAAGAAGGTRGATTGAUARGUUT AARGTRGUAUAGUAATTTAGT 164 AUTAAATTGUTGTGRGARGTTAGGRGTGTUAATRGAUUTTUTTGAGTGTUAGATTTT TUARGGUAUTGAGGGUTGAGAGGTAUUTTUTGGUARGAUAUAGAUUATGGUAGRG GATGTGGUUUATGGGAGAGGTTATUTUUURGGTUUTTXGUUTUTAUUTAGGAGGGU UTTUUUUAUAGAAGUAATAAGGGGUTTAAGGGAAAGGAGGUUAGGAGUTTUUUUT RGGTTTAUURGGUUAGRGAGGGUUAAGUAGRGGUTUTRGGUTUUTAGAGRGUTGRG RGUTUUUAGGRGGGUTUUTGG 165 GAGGUARGAAGUTGURGGAGUTAUTUAGUTTTAUUTUTAGGAAAGATAUAGRGAAT UAURGUUAATAAAAUAAAGUAAAAUAAAAAGUTRGUUATGUTGAARGGAATGGGA AAATTGUTUTUTTGTUAUTAATTTTGATTGAATTGAGTXGGUAATUTUTGAAURGGT TUAUTGATAUAAUAATAGGAAAUATTTAAUTGTTTUTTGUAUUTTTAAAUATAAATA GTAGGTTTTTAAGUAGTUAGTAGGRGATGTGTGATUAAGGTTUAGAUAGARGUAGA UAAUTGATUAUUUAUTUAG 166 UTGAGTGGGTGATUAGTTGTUTGRGTUTGTUTGAAUUTTGATUAUAUATRGUUTAUT GAUTGUTTAAAAAUUTAUTATTTATGTTTAAAGGTGUAAGAAAUAGTTAAATGTTTU UTATTGTTGTATUAGTGAAURGGTTUAGAGATTGUXGAUTUAATTUAATUAAAATTA GTGAUAAGAGAGUAATTTTUUUATTURGTTUAGUATGGRGAGUTTTTTGTTTTGUTT TGTTTTATTGGRGGTGATTRGUTGTATUTTTUUTAGAGGTAAAGUTGAGTAGUTURG GUAGUTTRGTGUUT 167 GAUUTUAGUTURGGGTGAUAURGGTGGGRGTRGGGTGTGGUUTUAGAUAGUTUUUT TUUTUUURGGUTGGTTGUUAGGTUAAUAURGGGTGGGAUTAGUUTUTGGTGTRGGU AGTAGUUUUATGUTUURGGUUTTTGGGTTUTTGUATGXGURGTUUUUATUAUUTGG UTGUUUUTUTUAUTTURGTUTUUAUUTGTUURGGGTUAUUTGTUUTTUAAGUUAGA AATTAAGGAUAGUAUUUUUTUUUAGAURGUUTGGUTGUAGTUURGGGATGGGRGU TUUTAGTRGUUTAGATRGGGU 168 GUURGATUTAGGRGAUTAGGAGRGUUUATUURGGGAUTGUAGUUAGGRGGTUTGG GAGGGGGTGUTGTUUTTAATTTUTGGUTTGAAGGAUAGGTGAUURGGGAUAGGTGG AGARGGAAGTGAGAGGGGUAGUUAGGTGATGGGGARGGXGUATGUAAGAAUUUAA AGGURGGGAGUATGGGGUTAUTGURGAUAUUAGAGGUTAGTUUUAUURGGTGTTG AUUTGGUAAUUAGURGGGGAGGAAGGGAGUTGTUTGAGGUUAUAUURGARGUUUA URGGTGTUAUURGGAGUTGAGGTU 169 GTATUTGTGTUAAUUAGRGGTTUTUAGUUTGGUUTUATUUAGGGUUTGAAGUUTAU TAUAGAAUUUUUAGUAGUARGTGGGGTGUAUAGUAAAGATUAGUUUTGGAUAUAG URGGGTGUTUAGGGRGGGGTGAGGGGGUAGGAGGUAGGAXGUAGGAGGTGAGUTG TURGGGRGGGGUAGGATGAGGGAGTUUTGUATTGUAGAGUTAAGGGGGAGAATUA TUAGUAUUUTAATTAGUTTTTTGATGGUTTUUAAAGUUTTTTAAGTUUTTTTTTTTTTT TTTTTTTTTTATUUUTAUAAG 170 UTTGTAGGGATAAAAAAAAAAAAAAAAAAAAAGGAUTTAAAAGGUTTTGGAAGUU ATUAAGAGUTAATTAGGGTGUTGATGATTUTUUUUUTTAGUTUTGUAATGUAGGAU TUUUTUATUUTGUUURGUURGGAUAGUTUAUUTUUTGXGTUUTGUUTUUTGUUUUU TUAUUURGUUUTGAGUAUURGGUTGTGTUUAGGGUTGATUTTTGUTGTGUAUUUUA RGTGUTGUTGGGGGTTUTGTAGTAGGUTTUAGGUUUTGGATGAGGUUAGGUTGAGA AURGUTGGTTGAUAUAGATAU 171 GATTAAUTTGUUTUUTGAUAAGTUATAUUUTTTAGUTTAGTAUTAAGGUAGAAGAG AGUUUTGTTGAAGAGUURGUTTGTGTTUTGTGGTAAAGAUAUAGGUUTAURGGUTT UTUXGTGGGTUUUAGTGUTGAGAAGGGUAUAGGUTGGUTGGAGAUAGTGUUUTGU TTGAUAGAUUUUTUUAXGUTRGGATUUTTUUAGTUTGUAURGGUUAUUTGUAUTGG TTTUARGGAAGAGUTAGAATTUTGTTTTAATGTTGGUUAGTTTUUATUATTAGUTTG AAAAGAAUAUAGAAUTTARG 172 RGTAAGTTUTGTGTTUTTUUAAGUTAATGATGGAAAUTGGUUAAUATTAAAAUAGA ATTUTAGUTUTTURGTGAAAUUAGTGUAGGTGGURGGTGUAGAUTGGAAGGATURG AGXGTGGAGGGGTUTGTUAAGUAGGGUAUTGTUTUUAGUUAGUUTGTGUUUTTUTU AGUAUTGGGAUUUAXGGAGAAGURGGTAGGUUTGTGTUTTTAUUAUAGAAUAUAA GRGGGUTUTTUAAUAGGGUTUTUTTUTGUUTTAGTAUTAAGUTAAAGGGTATGAUTT GTUAGGAGGUAAGTTAATU 173 GAUUAUAGGTGTGTGUTATUATGUURGGGTAATTTTTATATTTTTTGGTUTUAUTAT GTTGUUUAGGUTGGTUTUAAAUTUUTGGGUTUAAGTGATUUTUUTGUUTUAGUUTU UUAAAGTGTTGGATTAGAGGUATGAGUUAUUTTGUAXGTTTGUUTUUTGAUUTUAG GTUUUUARGGAGTTGGTUATUTTUTGGGUUTRGUTUAGURGGTGUTGAAGGTGAGT UATGUTRGATGATGAUUTGAGGAGUAGAAGAAGGTGUAGGTGAGTUAUUTGAGGG GAAUTGGGTUATGAUUAGAG 174 UTUTGGTUATGAUUUAGTTUUUUTUAGGTGAUTUAUUTGUAUUTTUTTUTGUTUUT UAGGTUATUATRGAGUATGAUTUAUUTTUAGUAURGGUTGAGRGAGGUUUAGAAG ATGAUUAAUTURGTGGGGAUUTGAGGTUAGGAGGUAAAXGTGUAAGGTGGUTUAT GUUTUTAATUUAAUAUTTTGGGAGGUTGAGGUAGGAGGATUAUTTGAGUUUAGGA GTTTGAGAUUAGUUTGGGUAAUATAGTGAGAUUAAAAAATATAAAAATTAUURGG GUATGATAGUAUAUAUUTGTGGTU 175 AGGAAGTRGAGGUTTAGAAGTTGGGTGAUTTGTUAAAGGTRGUUAUUUARGGTGAG GGUUAGGTTUTGGGAGGGUTGAGGGGUAGGUATGGTGAGUUAGTTURGGGUATGA GGUAAGGRGTGGUAGGUUTGGGGGUAAAAGUUAUAGUUXGTGTGGAGGGGGTGGG GGGATRGAGGUUTTTGGGAAGUUTGTGGATTUTGGUTGUAGTGTGGGTGTGAUAUT GAGTGUTURGGGGAUTURGAGTTATUAUUUAGGUAUTGGUUAGUUUUARGUTUUU TUUTUUAGGTAUTTGGUTUUUTG 176 AGGGAGUUAAGTAUUTGGAGGAGGGAGRGTGGGGUTGGUUAGTGUUTGGGTGATA AUTRGGAGTUUURGGAGUAUTUAGTGTUAUAUUUAUAUTGUAGUUAGAATUUAUA GGUTTUUUAAAGGUUTRGATUUUUUUAUUUUUTUUAUAXGGGUTGTGGUTTTTGUU UUUAGGUUTGUUARGUUTTGUUTUATGUURGGAAUTGGUTUAUUATGUUTGUUUUT UAGUUUTUUUAGAAUUTGGUUUTUAURGTGGGTGGRGAUUTTTGAUAAGTUAUUU AAUTTUTAAGUUTRGAUTTUUTU 177 AGUUARGGRGAUUAUUAUUTUUATUUTUUUUUAUUTUUTUUTUUTGUAGGTGGUU TTTTTGGUUAGTGTGTUTGAGTGUTUAUUTUTTGUTUTAGTGTUUTGGTGUTURGGUT UTUUTUTTUUTUUTUAUTUTUUTGGGUUTGGGUUTGUXGUTUURGGGUUTUUAGGT UTAGAUAUAAGGGTTGAATGAUUAGAUTGUTGGTUTGTTUAGTTTUUATGTGGUUT RGGUUUAUUUUAGUTUTGGUTGUUTUUUUAAAGTUTUAATUARGARGAGATUATA UAGTAAUTUTGUUUUUTUUUT 178 AGGGAGGGGGUAGAGTTAUTGTATGATUTRGTRGTGATTGAGAUTTTGGGGAGGUA GUUAGAGUTGGGGTGGGURGAGGUUAUATGGAAAUTGAAUAGAUUAGUAGTUTGG TUATTUAAUUUTTGTGTUTAGAUUTGGAGGUURGGGAGXGGUAGGUUUAGGUUUA GGAGAGTGAGGAGGAAGAGGAGAGURGGAGUAUUAGGAUAUTAGAGUAAGAGGT GAGUAUTUAGGUAUAUTGGUUAGAAGGUUAUUTGUAGGAGGAGGAGGTGGGGGA GGATGGAUUTGGTGGTRGURGTGGUT 179 AAGGTGAATGUTGUAAUUUTUTUTUUTUAGUUUTGUAGURGATUUUTGAUATAAAU TUUTTGAAGTTUAGTGGUUTUTTTUUATGUAUUTAUUAUUTAUAUUTGUTGU AAGAAAUUAUAAUUTGGAURGGGAAUAGAAUTGGAXGTGUUAAAATGUUTGAGGA UAUTTUATXGAATGTGGUTGGUTTGATGGGAAGUTGGUATGAUTAGAAATGTUAGG AGTUTTUUUTUTXGAGGTTTUAAGUTTTGTGTTTUTGAUTUAATGGTURGGATTGAG

ATUAGATGAGTUAAGTTUA 180 GAAUTTGAUTUATUTGATUTUAATURGGAUUATTGAGTUAGAAAUAUAAAGUTTGA AAUUTXGAGAGGGAAGAUTUUTGAUATTTUTAGTUATGUUAGUTTUUUATUAAGUU AGUUAUATTXGATGAAGTGTUUTUAGGUATTTTGGUAXGTUUAGTTUTGTTUURGGT UUAGGTTGTGGTTTUTTTGAAAGUAGUAGGTGTAGGTGGTAGGTGUATGGAAAGAG GUUAUTGAAUTTUAAGGAGTTTATGTUAGGGATRGGUTGUAGGGUTGAGGAGAGAG GGTTGUAGUATTUAUUTTU 181 UAGUUUTGUAGURGATUUUTGAUATAAAUTUUTTGAAGTTUAGTGGUUTUTTTUUA TGUAUUTAUUAUUTAUAUUTGUTGUTTTUAAAGAAAUUAUAAUUTGGAURGGGAA UAGAAUTGGAXGTGUUAAAATGUUTGAGGAUAUTTUATXGAATGTGGUTGGUTTGA TGGGAAGUTGGUATGAUTAGAAATGTUAGGAGTUTTUUUTUTXGAGGTTTUAAGUT TTGTGTTTUTGAUTUAATGGTURGGATTGAGATUAGATGAGTUAAGTTUAGATGAUU ATGUAAAUUTTTAGATGGGG 182 UUUUATUTAAAGGTTTGUATGGTUATUTGAAUTTGAUTUATUTGATUTUAATURGGA UUATTGAGTUAGAAAUAUAAAGUTTGAAAUUTXGAGAGGGAAGAUTUUTGAUATTT UTAGTUATGUUAGUTTUUUATUAAGUUAGUUAUATTXGATGAAGTGTUUTUAGGUA TTTTGGUAXGTUUAGTTUTGTTUURGGTUUAGGTTGTGGTTTUTTTGAAAGUAGUAG GTGTAGGTGGTAGGTGUATGGAAAGAGGUUAUTGAAUTTUAAGGAGTTTATGTUAG GGATRGGUTGUAGGGUTG 183 UUTAUUAUUTAUAUUTGUTGUTTTUAAAGAAAUUAUAAUUTGGAURGGGAAUAGAAUTGGA XGTGUUAAAATGUUTGAGGAUAUTTUATXGAATGTGGUTGGUTTGATGGGAAGUTGGUATG AUTAGAAATGTUAGGAGTUTTUUUTUTXGAGGTTTUAAGUTTTGTGTTTUTGAUTUAATGGTU RGGATTGAGATUAGATGAGTUAAGTTUAGATGAUUATGUAAAUUTTTAGATGGGGUUTAAAA UUAAATUTGTGTTUTTAAAUUATTUUAAATGTGTTUATUAUUAGTTATAGTTT 184 AAAUTATAAUTGGTGATGAAUAUATTTGGAATGGTTTGAGAAUAUAGATTTGGTTTTAGGUU UUATUTAAAGGTTTGUATGGTUATUTGAAUTTGAUTUATUTGATUTUAATURGGAUUATTGA GTUAGAAAUAUAAAGUTTGAAAUUTXGAGAGGGAAGAUTUUTGAUATTTUTAGTUATGUUA GUTTUUUATUAAGUUAGUUAUATTXGATGAAGTGTUUTUAGGUATTTTGGUAXGTUUAGTTU TGTTUURGGTUUAGGTTGTGGTTTUTTTGAAAGUAGUAGGTGTAGGTGGTAGG 185 GAGAGGGGAAGGGGURGAUUAUUTGUTUURGAGUUATTUTRGGGUTRGGUUAGUU ATTGGGUTGGGAAUUTGTUAATUUTGGTTGATUTTUUAATGAGUTGTGAAUTGGTUT TURGGGAGGAUTTAUAGGAGGUTGGAAARGGGGUUTGGXGRGRGUTTUUUTUTUAG TGRGAGGUTGAUTGGTTGGAUTRGURGGGUTUTAUTGTGGGUUUUARGUTATGTTT AGARGUURGARGTGTUUUATTTTATTGAAUTRGTUUTGUUUUUUAAGTAGGGARGA TTTAUUTUUATTTTUTAGAT 186 ATUTAGAAAATGGAGGTAAATRGTUUUTAUTTGGGGGGUAGGARGAGTTUAATAAA ATGGGAUARGTRGGGRGTUTAAAUATAGRGTGGGGUUUAUAGTAGAGUURGGRGA GTUUAAUUAGTUAGUUTRGUAUTGAGAGGGAAGRGRGXGUUAGGUUURGTTTUUA GUUTUUTGTAAGTUUTUURGGAAGAUUAGTTUAUAGUTUATTGGAAGATUAAUUAG GATTGAUAGGTTUUUAGUUUAATGGUTGGURGAGUURGAGAATGGUTRGGGAGUA GGTGGTRGGUUUUTTUUUUTUTU 187 RGGGGGUAGGGAGUAGAUUTGAUTUAGTGGRGTUAGTGUTAUTTUAAAGRGGUAG RGUATTTUATTAAAAATUTGATGTAGAAATTAUUUTGGGUTTTGTTTTGUAAAGAGU ATTTGUATAAGAAAAAATAATUAGURGGTTAATTUUUUXGTUUAUTGGUAGGAAGA GAGAUAGUUTTUAGAGAGTTTGGGAUTUTUTUATTUURGGAGAATTAAAAGUUTUR GAGAUATUUATTTTAGAAGTTUTGGTUAATRGTTUTTAAAGTGRGGTUAGAAGAUU UUTTGRGTUTGAATGGTTTG 188 UAAAUUATTUAGARGUAAGGGGTUTTUTGAURGUAUTTTAAGAARGATTGAUUAGA AUTTUTAAAATGGATGTUTRGGAGGUTTTTAATTUTURGGGAATGAGAGAGTUUUA AAUTUTUTGAAGGUTGTUTUTUTTUUTGUUAGTGGAXGGGGGAATTAAURGGUTGA TTATTTTTTUTTATGUAAATGUTUTTTGUAAAAUAAAGUUUAGGGTAATTTUTAUAT UAGATTTTTAATGAAATGRGUTGURGUTTTGAAGTAGUAUTGARGUUAUTGAGTUA GGTUTGUTUUUTGUUUURG 189 UAGTGTTGTAGAUUTATTAATTATUAGGATAATTARGGARGGGGAAATUUAGAUAU AGATAUAATUAGTGUUUTUUTUUAUUTUUURGUAUARGUUUUTUURGGTUTUUUTG AUATUUTGGTGTGUAUTGTGTTUUUUTGUUATUTUUAXGUTGRGGUTUUTAUTAGA UUUAUUUUTGURGGTGUUAAAATGUUUAAAGGAAGGUTGAGTUATGUTUTGGUUT GUUUAGURGUAATAGTUATGUTGUAAUTUUUARGGAAAAUUTUUTTTUAUUUAUTU UAGAGGTUTGAGAUAUUUTAA 190 TTAGGGTGTUTUAGAUUTUTGGAGTGGGTGAAAGGAGGTTTTURGTGGGAGTTGUA GUATGAUTATTGRGGUTGGGUAGGUUAGAGUATGAUTUAGUUTTUUTTTGGGUATT TTGGUAURGGUAGGGGTGGGTUTAGTAGGAGURGUAGXGTGGAGATGGUAGGGGA AUAUAGTGUAUAUUAGGATGTUAGGGAGAURGGGAGGGGRGTGTGRGGGGAGGTG GAGGAGGGUAUTGATTGTATUTGTGTUTGGATTTUUURGTURGTAATTATUUTGATA ATTAATAGGTUTAUAAUAUTG 191 GGAAGGAGRGAGUTTUTTTTTATAGGAGUTUUAGTTUUTRGTTTTGTTUTUTTRG TTATTUTUUAAAGAAAGURGGUTUTTGAGTUAGUTGGUAGGAGAGRGAGGRGAATG RGUTGGTGUTGGURGUAATGGUUURGGTTUAARGUTXGUTUUAGUTGGTUARGTUU TUAURGGGGRGGURGGRGGUUTGUUTGUUUARGUTUTGUUAGGAGUUUAGGTUAG UUUrrGUUTRGURGGGGURGGAGUURGTUUAAAATUAAUAAGTUTTTTGTGUUTUT UUTTTGGARGUTGTATAATT 192 AATTATAUAGRGTUUAAAGGAGAGGUAUAAAAGAUTTGTTGATTTTGGARGGGUTU RGGUUURGGRGAGGUAAGGGUTGAUUTGGGUTUUTGGUAGAGRGTGGGUAGGUAG GURGURGGURGUUURGGTGAGGARGTGAUUAGUTGGAGXGAGRGTTGAAURGGGG UUATTGRGGUUAGUAUUAGRGUATTRGUUTRGUTUTUUTGUUAGUTGAUTUAAGAG URGGUTTTUTTTGGAGAATAAUURGAAGAGAAUAAAARGAGGAAUTGGAGUTUUTA TAAAAAGAAGUTRGUTUUTTUU 193 UTGGTTGTGGAAGGAGRGAGUTUTURGTUUURGGGAGTATGUAAGTTTUUUUTUUA RGATUAUTTGGAAGGGATTGGGRGGAGTTUTGTUATTTGGAGAAAGGGTUUTGGGA GUTTUAGGTTTGTGTAGGGRGAGGARGGGGRGGTTUTGXGTURGGUUAGGTTGGUU UTRGAGGAUUUAGURGTUUUUAAUUTUUTAAAUTGUTGTRGGATGTAGAAGAUTRG UATTUAUTGUTUTUUAUAGTRGGTGAAGGGAGAARGURGAAAAGGGURGUATTUUU TUUTGURGGTUUUUTUUUUT 194 AGGGGAGGGGAURGGUAGGAGGGAATGRGGUUUTTTTRGGRGTTUTUUUTTUAURG AUTGTGGAGAGUAGTGAATGRGAGTUTTUTAUATURGAUAGUAGTTTAGGAGGTTG GGGARGGUTGGGTUUTRGAGGGUUAAUUTGGURGGAXGUAGAAURGUUURGTUUT RGUUUTAUAUAAAUUTGAAGUTUUUAGGAUUUTTTUTUUAAATGAUAGAAUTURG UUUAATUUUTTUUAAGTGATRGTGUAGUUUAAAUTTGUATAUTUURGGGGARGGAG AGUTRGUTUUTTUUAUAAUUAG 195 GGGTGTUAGGUTAUUUTTGAAGGGAUUTAUUTUUTUUAGUUAUTGUUAUTGGAUU UTUUUTUAGUUUUTUTAGUAAAGUAGUUUUAATGUATGTUUTGAGATTGTUURGGA AAAUTGTUAUTUAGAGGGGAAGAUTUTTGGGUAUAGAGUXGTTATTTATAAUAGUA AGAUAUTGUAGGUTGUUTAAAUAUTUUARGAUAGAGATGARGGAGUAATTUARGG UAUUUUTGUUAAGAGAGTATTAUAUAGUUATTAAAAATGATUAAGUAGAGAURGG TAGTGARGUTGAGTAATGTTTTU 196 GAAAAUATTAUTUAGRGTUAUTAURGGTUTUTGUTTGATUATTTTTAATGGUTGTGT AATAUTUTUTTGGUAGGGGTGURGTGAATTGUTURGTUATUTUTGTRGTGGAGTGTT TAGGUAGUUTGUAGTGTUTTGUTGTTATAAATAAXGGUTUTGTGUUUAAGAGTUTT UUUUTUTGAGTGAUAGTTTTURGGGAUAATUTUAGGAUATGUATTGGGGUTGUTTT GUTAGAGGGGUTGAGGGAGGGTUUAGTGGUAGTGGUTGGAGGAGGTAGGTUUUTT UAAGGGTAGUUTGAUAUUU 197 GUUUAURGRGGAGGGUUUUUUTATUUTUUTUATUUTUAUTGGUTUAUUUAGGGUA UUAUUAUUTUUTUUAGGAAAUUUTUUUTGUUUUUTATUTUTGGGTGTUTUAUAUUU TGGGUAUUTAUAGUUAGAAUUUUAUUTURGGGUUUTUXGTTTUUAGTGGUTGAGT AGGAGUTTUAGTTTTAGGAGAUTUUUUTGAGUAGAAURGAUUUUTUTTUATUTTUU UAAUUUUUAUUUAUAUAUTUAGGAUTGGGTAURGGGGUUTGUUUUAATTTGUAGG UTTAGAGTUAGGGGTTAGGGTGG 198 UAUUUTAAUUUUTGAUTUTAAGUUTGUAAATTGGGGUAGGUUURGGTAUUUAGTU UTGAGTGTGTGGGTGGGGGTTGGGAAGATGAAGAGGGGTRGGTTUTGUTUAGGGGA GTUTUUTAAAAUTGAAGUTUUTAUTUAGUUAUTGGAAAXGGAGGGUURGGAGGTG GGGTTUTGGUTGTAGGTGUUUAGGGTGTGAGAUAUUUAGAGATAGGGGGUAGGGA GGGTTTUUTGGAGGAGGTGGTGGTGUUUTGGGTGAGUUAGTGAGGATGAGGAGGAT AGGGGGGUUUTURGRGGTGGGUA 199 UTTAAATGAGAAGAAUATGTTTUTAUAURGUATTTGTGAAAGTTTGGUTRGGAGUTA RGRGUTGATTAATATUAGATUTUUTTUAUTRGUUTRGUUAUAATUTTGTUAUATUTG GUTGAUAAATUURGAGGAAUTURGGUAAAGUUAGGXGGRGGRGGGGUTURGGGTU TGGGRGGRGGUTURGGAGGAGUAGRGGGAGAUUURGUAGRGGUUTUUTUUTTUTU RGUURGRGGUUUUUAGUUTRGURGURGURGUURGGUTUUUAGUARGGAAURGARG GGGRGUTUURGAGARGGGRGA 200 TRGUURGTUTRGGGAGRGUUURGTRGGTTURGTGUTGGGAGURGGGRGGRGGRGGR GAGGUTGGGGGURGRGGGRGGAGAAGGAGGAGGURGUTGRGGGGTUTUURGUTGU TUUTURGGAGURGURGUUUAGAUURGGAGUUURGURGUXGUUTGGUTTTGURGGA GTTUUTRGGGATTTGTUAGUUAGATGTGAUAAGATTGTGGRGAGGRGAGTGAAGGA GATUTGATATTAATUAGRGRGTAGUTURGAGUUAAAUTTTUAUAAATGRGGTGTAG AAAUATGTTUTTUTUATTTAAG 201 GTGGTAGGTUTGTGTGGAGAUTTGAATUUTGTTTTUTUUUAGUUTTTTUUAUUAAGG AUAUUUAGGAGAGUAAGGATATGGUUAGAGGAGAGGTGGTGTTUUUUTUTTGAUT GGGUUUTGUTUTUAGUUUUAUAGGTGATURGGAAGATTXGGGTGGAGUAGTTTUUT GATGUUTURGGTAGUUTGAAGUTGTGGTGUUAGTTTTTUAAUATTUTTAGTGAUTUA GTUTTGAUATGGGUUAAGGATUAGRGUUUAGTGGGRGAGGTGGGUAGGAGGTAAG UUAARGAUAUUAUTGUUAUU 202 GGTGGUAGTGGTGTRGTTGGUTTAUUTUUTGUUUAUUTRGUUUAUTGGGRGUTGAT UUTTGGUUUATGTUAAGAUTGAGTUAUTAAGAATGTTGAAAAAUTGGUAUUAUAGU TTUAGGUTAURGGAGGUATUAGGAAAUTGUTUUAUUXGAATUTTURGGATUAUUTG TGGGGUTGAGAGUAGGGUUUAGTUAAGAGGGGAAUAUUAUUTUTUUTUTGGUUAT ATUUTTGUTUTUUTGGGTGTUUTTGGTGGAAAAGGUTGGGAGAAAAUAGGATTUAA GTUTUUAUAUAGAUUTAUUAU 203 TGUUTAUUAUAUUTRGTGGGTGAAAUAGATATTTRGAGUATGAUTGAGUTTATTAA GAGUUUTGRGGRGUTTUUTUTGURGGGGGTTTAGAAATTTUAAAGGATGGGGGTTG AGGGAGGGAGGAGTTATGGGUATGTGATGTGGAUAGGGXGGGUAGGAGGATGGAA GTAAUAGGTUUAAAATGTATUTTTGGTGGUURGGUAGAGUTUTTGUATGGGGTGAG AATGGTAATTTAGGAAGAGUAAGTUTTUUUATUTGTGAAGUAGAAGAAAAAAGTGG AUTTAAGGAGAAGTTRGGGTG 204 UAUURGAAUTTUTUUTTAAGTUUAUTTTTTTUTTUTGUTTUAUAGATGGGAAGAUTT GUTUTTUUTAAATTAUUATTUTUAUUUUATGUAAGAGUTUTGURGGGUUAUUAAAG ATAUATTTTGGAUUTGTTAUTTUUATUUTUUTGUUXGUUUTGTUUAUATUAUATGU UUATAAUTUUTUUUTUUUTUAAUUUUUATUUTTGAAATTTUTAAAUUUURGGUAG AGGAAGRGURGUAGGGUTUTTAATAAGUTUAGTUATGUTRGAAATATUTGTTTUAU UUARGAGGTGTGGTAGGUA 205 GAGUUAAUUTUTUUTTTUATTUUTGGAGGTGGGGGAUURGUUUTUATUTUAGGUUT GAAGAGGGUTGTGTGTGAGTTUTUUAUTTGTGTGTGGGGTGAGUURGGUUUATGUA UAUAGUTAUAUAUAUATUAUAUAUUUAUAUURGGAUAXGRGUUTUAGGTUUUUAU AUTGUUUTTAUAUAUATGRGUUUUTUAUAUATGUATGTUUUUTTTGUAUAUARGUU UUUTRGUAUARGUATGUUUUUTRGUAUARGUATGUAUAUAGGUTUAUTUTGUTGU UTGTUUUTGGUTGUTGTGTGUT 206 AGUAUAUAGUAGUUAGGGAUAGGUAGUAGAGTGAGUUTGTGTGUATGRGTGTGRG AGGGGGUATGRGTGTGRGAGGGGGRGTGTGTGUAAAGGGGAUATGUATGTGTGAGG GGRGUATGTGTGTAAGGGUAGTGTGGGGAUUTGAGGRGXGTGTURGGGTGTGGGTG TGTGATGTGTGTGTAGUTGTGTGUATGGGURGGGUTUAUUUUAUAUAUAAGTGGAG AAUTUAUAUAUAGUUUTUTTUAGGUUTGAGATGAGGGRGGGTUUUUUAUUTUUAG GAATGAAAGGAGAGGTTGGUTU 207 UUUARGGGGGUAGGUAURGGAGGGGGTGUUUAUAGAGGATAGAGGARGURGAGA AGTGAUUTGGGGAGUUATAGGATGAGGAAGAGAGAAGAGATGAUAGUAGGGGUTG TAGGAGGTUAUUUTUUARGGAGGGAGGGGTGARGGUAGAGGXGTURGUAGGAGUT GGTAURGGTGGGGUTGUUUUUAGGGGGGGUTGAUAGAGGUAGUAAUTGAGUAGGU AGGGGTGGAGRGAGGTGUUAGUUTGURGTGGAAAGGAGARGUUAGUAGRGGGGGG UUUTUUTGGGGTUUUAGTUUTGUTUT 208 AGAGUAGGAUTGGGAUUUUAGGAGGGUUUUURGUTGUTGGRGTUTUUTTTUUARG GUAGGUTGGUAUUTRGUTUUAUUUUTGUUTGUTUAGTTGUTGUUTUTGTUAGUUUU UUUTGGGGGUAGUUUUAURGGTAUUAGUTUUTGRGGAXGUUTUTGURGTUAUUUU TUUUTURGTGGAGGGTGAUUTUUTAUAGUUUUTGUTGTUATUTUTTUTUTUTTUUTU ATUUTATGGUTUUUUAGGTUAUTTUTRGGRGTUUTUTATUUTUTGTGGGUAUUUUU TURGGTGUUTGUUUURGTGGG 209 TGAUAUTUAGGATUUAAAAGUTAGUUUTGUUUAUUUUAGUUUUTUUAUUTUUTTA UUTGGGTGTGUAUUTGUTURGGGGGGTGGAGGTGUTUUUUAUAGTURGGGUUAGG AUAGUUTUAGGGGAGAGTGAAGGUUTGUAGGAGGGUAGGXGAGAUAAGGAGGGT GTUUAGGGUTAGGGAGTGURGGATGAAAUUAGUTUTGTUUUTGTGUAGGUTUUAG GUTUURGUUTGAUAAAUAGGUAGGGAGUUAUAGTUAGGGAUAATAAAAAUTTGGT GUAUTUTGAAAGUAGUAUTTGGAUAG 210 TGTUUAAGTGUTGUTTTUAGAGTGUAUUAAGTTTTTATTGTUUUTGAUTGTGGUT UTGUUTGTTTGTUAGGRGGGAGUUTGGAGUUTGUAUAGGGAUAGAGUTGGTTTUAT URGGUAUTUUUTAGUUUTGGAUAUUUTUUTTGTUTXGUUTGUUUTUUTGUAGGUUT TUAUTUTUUUUTGAGGUTGTUUTGGUURGGAUTGTGGGGAGUAUUTUUAUUUUURG GAGUAGGTGUAUAUUUAGGTAAGUAGGTUUAGGGGUTGGGGTGGGUAGGGUTAGU TTTTGGATUUTGAGTGTUAU 211 UAAATAAGTAGTTAUUTUAGAAGTUAUTTARGTAAAAGAUTUATTUUUUAAAARGU UAGGUAUATGGATTATUAUTGTGTTATTUAARGARGATAUAATGGUAUAGAATGTA TUATAUTGAGAAGTGAGTGUUUTUTURGGGAUATAUTXGTUAGTGAGTUATUUAGU AUTAGAAUAUTGGAGATATAAATAAATAUUAUUTUTTUTAAAAUAGTUTGAAATTU AAGTGGTUATAAUUTAGAGUATUATGGURGGGUATGGTGGUTUATGUUTGTAAUUU UAGUATGAGGUTGAGATGGG 212 UUATUTUAGUUTUATGUTGGGGTTAUAGGUATGAGUUAUUATGUURGGUUATGATG UTUTAGGTTATGAUUAUTTGAATTTUAGAUTGTTTTAGAAGAGGTGGTATTTATTTAT ATUTUUAGTGTTUTAGTGUTGGATGAUTUAUTGAXGAGTATGTUURGGAGAGGGUA UTUAUTTUTUAGTATGATAUA1TUTGTGUUATTGTATRGTRGTTGAATAAUAUAGTG ATAATUUATGTGUUTGGRGTTTTGGGGAATGAGTUTTTTARGTAAGTGAUTTUTGAG GTAAUTAUTTATTTGA 213 GTUUTUAUATTTGAUTURGGATAAAUUTUTTUAAATATTTTAUAGAUTUTGGUTTTU TRGTTAAUAAGUAGUTUAUAUATATAGTGTUTUAGUAGTGAUAGATGUTGGUUUAU UURGAGGTUAGGATGAUTUAGUAGGGATTGAGTTTGXGGGRGTUATGUTUUAAGGU URGGAATAGGAGUTTGGTGUTUATTUUTUAUATAGTGGGUAAATUUTAGGGUAGGG GAGGGGGGGUAATGUUAGAGAATGGTUUUUAUUTGGGGRGGTUTGARGGUUAGAG ATGUAGAGAAAGAGARGUUT 214 AGGRGTUTUTTTUTUTGUATUTUTGGURGTUAGAURGUUUUAGGTGGGGAUUATTU TUTGGUATTGUUUUUUUTUUUUTGUUUTAGGATTTGUUUAUTATGTGAGGAATGAG UAUUAAUUTUUTATTURGGGUUTTGGAGUATGARGUUXGUAAAUTUAATUUUTGUT GAGTUATUUTGAUUTRGGGGTGGGUUAGUATUTGTUAUTGUTGAGAUAUTATATGT GTGAGUTGUTTGTTAARGAGAAAGUUAGAGTUTGTAAAATATTTGAAGAGGTTTATU RGGAGTUAAATGTGAGGAU 215 GAAAGUAGUUUTUTUUUTGUUUTGTAAGGTGATUUURGATURGGGAATTUUUAUTT UTGAAGGARGTTUTGGAAAAGTGUAUAGATTAAUTGAGATTUUTGUTTUTGGATUA AGUAUTUUTGAUAUTATXGTTURGATTTTUTAAAAAAGAGATTGTGGUAAAATUTA UUTXGTGAGATUAGAAAATGUAGUAGGGATGAATUAURGGUUUTUTUAGAUUTUA UUAGUUTUUAGGUUATTUUTAAGAGUUTUAUTUUTURGTTUTGTTGGUAGTGGGGG AGGTARGGGGURGGATGGUA

216 TGUUATURGGUUURGTAUUTUUUUUAUTGUUAAUAGAARGGAGGAGTGAGGUTUT TAGGAATGGUUTGGAGGUTGGTGAGGTUTGAGAGGGURGGTGATTUATUUUTGUTG UATTTTUTGATUTUAUXGAGGTAGATTTTGUUAUAATUTUTTTTTTAGAAAATRGGA AXGATAGTGTUAGGAGTGUTrGATUUAGAAGUAGGAATUTUAGTTAATUTGTGUAU TTTTUUAGAARGTUUTTUAGAAGTGGGAATTUURGGATRGGGGATUAUUTTAUAGG GUAGGGAGAGGGUTGUTTTU 217 AAGAAAAGAGAAAGUUUATUUAGGTAAGGGUAGUUTGGTGAUTATTAUUUTGGGGAGAUTU UUUAUUUAUAUTGUUAUTUUAGGUTUAUURGAGGGUTGUAGUTTUUTURGGATGGATUUAG GGXGGUTAUTGGTUUUAGAGUTGGGGGUTGAGTGGGUURGTGUXGAGGGUTGTGGXGTUTG AUAAGURGGUTUUUAUTGTGAGUAGGGAAGGGRGGATGGGRGGGGGUUARGGUTGUUUTGG UTUUUUAUUUTGUTGTGUTTUTUTUTAUTUUUUTGUUUTGUUTUUTAAUAUUUAGT 218 AUTGGGTGTTAGGAGGUAGGGUAGGGGAGTAGAGAGAAGUAUAGUAGGGTGGGGAGUUAG GGUAGURGTGGUUUURGUUUATURGUUUTTUUUTGUTUAUAGTGGGAGURGGUTTGTUAGA XGUUAUAGUUUTXGGUARGGGUUUAUTUAGUUUUUAGUTUTGGGAUUAGTAGUXGUUUTG GATUUATURGGAGGAAGUTGUAGUUUTRGGGTGAGUUTGGAGTGGUAGTGTGGGTGGGGAG TUTUUUUAGGGTAATAGTUAUUAGGUTGUUUTTAUUTGGATGGGUTTTUTUTTTTTTIT 219 UTGAGGUAGGGUTGUAGGUTUAGGAGGAGGAGATGGGTGGAGAGAGAAUAAGUTTT AUUURGGGAGGGTGAUTAUAGGAGAAATGGGUUUUTUAAGTATGUTGATTTUXGU UTUAUTGUTGUUTGTUUTUXGUUUAUUTURGGUTUTGGUTUATUTGUTUTTGTAAG UAGGGTUUTGGGUTGGGTGUTGUAGGXGUATGAGGAAAGTGGGAGURGGGARGGG GUAGUTUAGGGUARGUUUTUUAAUAUTGRGUTURGAGGAUUTUAGRGGTTTTAUTU AGGGGTGUUAUTGAGGUAUAGU 220 GUTGTGUUTUAGTGGUAUUUUTGAGTAAAAURGUTGAGGTUUTRGGAGRGUAGTGT TGGAGGGRGTGUUUTGAGUTGUUURGTUURGGUTUUUAUTTTUUTUATGXGUUTGU AGUAUUUAGUUUAGGAUUUTGUTTAUAAGAGUAGATGAGUUAGAGURGGAGGTGG GXGGAAGAGUAGGUAGUAGTGAGGXGGAAATUAGUATAUTTGAGGGGUUUATTTU TUUTGTAGTUAUUUTUURGGGGTGAGUTTGTTUTUTUTUUAUUUATUTUUTUUTUUT GAGUUTGUAGUUUTGUUTUAG 221 GUUUAGGUTGGAGTGUAGTGGRGTGATUTTGGUTUAUTGUAAUUTUTGUUTUURGG GTTUAAGRGATTUTULTTGUUTUAGUUTUUUAGATAUUTGGGATTAUAGGTGTGTGA UAUUATAUUUAGUTAATTTTTGTATTTTTAGTAGAGAXGGUUATGTTAGTUAGGUTG GTUTTGAAUTUUTGAUUTUAGTGATTUAURGGUUTUAGUUUUUAAAGTGUTGGTAT TATAGTUATGAGUUAUTGUAUURGGUUTUTGUTTTTGUTTUUTTAGTGGUATUUUAU TGUUTTGUTTTUAAUATT 222 AATGTTGAAAGUAAGGUAGTGGGATGUUAUTAAGGAAGUAAAAGUAGAGGURGGG TGUAGTGGUTUATGAUTATAATAUUAGUAUTTTGGGGGUTGAGGURGGTGAATUAU TGAGGTUAGGAGTTUAAGAUUAGUUTGAUTAAUATGGUXGTUTUTAUTAAAAATAU AAAAATTAGUTGGGTATGGTGTUAUAUAUUTGTAATUUUAGGTATUTGGGAGGUTG AGGUAGGAGAATRGUTTGAAUURGGGAGGUAGAGGTTGUAGTGAGUUAAGATUAR GUUAUTGUAUTUUAGUUTGGGU 223 GUUAUTUTATAAAAATGAAGAGUAGAGUTRGAGTGUTTATAAUARGTUATTTTTAU UUAAGAUAGAGAAGAAAAARGAAAGAGAGUUTGAGUATTUUTTTGAUTUUUTUUA UUUURGGAAGGTATATTUAGAGTUTUUAAGAUTGUUTUXGUUUAUTUAUATGTTrA TGGUURGGTGAGAURGUATUUTUUUTTTUTATATUTGTUUUTTTTUTGGATGUAGGG AUAUAGAATUUUUTAAGTGGGAAGAGUTTTGGAGTGGAGGUTGTTUAAAGTTUTGT GGTGATTAATTATTAUUTAU 224 TAGGTAATAATTAATUAUUAUAGAAUTTTGAAUAGUUTUUAUTUUAAAGUTUTTUU UAUTTAGGGGATTUTGTGTUUUTGUATUUAGAAAAGGGAUAGATATAGAAAGGGAG GATGRGGTUTUAURGGGUUATAAAUATGTGAGTGGGXGGAGGUAGTUTTGGAGAUT UTGAATATAUUTTURGGGGGTGGAGGGAGTUAAAGGAATGUTUAGGUTUTUTTTRG TTTTTUTTUTUTGTUTTGGGTAAAAATGARGTGTTATAAGUAUTRGAGUTUTGUTUTT UATTTTTATAGAGTGGUT 225 ATTAAAAUAGUAAAUTUUAGGUUUAAAGTAGGTTTUAGTUTUTATTAAGATAAUAA AAGGTUUTAAATGUUAGGUUTGGGRGUAAAUTGTGUAGAUAAGRGGGTGGURGGA GAAGGAGGGGGGTUAAGGAAGAGAGGGAAAUTUAATTGAXGGTTAUTTTTTTTTUA GAGTTATTTURGGTGGGTUTGUUUUUAUUUUTUAAUAAATTTTGTTGUTUTGA TUUAGGUATAAAAAGTGAGGUUUTGGAGGGUUUUTGAGAUUAGRGTUUTGUAUAG TGAUATGGUAUAGTGAUATGG 226 UUATGTUAUTGTGUUATGTUAUTGTGUAGGARGUTGGTUTUAGGGGUUUTUUAUUG UUTUAUTTTTTATGUUTGGAATGUUUAGAGUAAUAAAATTrGTTGAGGGGTGGGGG UAGAUUUAURGGAAATAAUTUTGAAAAAAAAGTAAUXGTUAATTGAGTTTUUUTUT UTTUUTTGAUUUUUUTUUTTUTURGGUUAUURGUTTGTUTGUAUAGTTTGRG GGUUTGGUATTTAGGAUUTTTTGTTAUTTTAATAGAGAUUGAAAUUTAUTTTGGGUU TGGAGTTTGUTGTTTTAAT 227 GGUTUTGAGAGTGUTGGAAUUAAURGGARGGGGTUAGUUUUAUUATGGGAUUTGG URGATGAGTUATUTUTUTGAAGGRGTUTTUUUTTUTGTGAAGTGGGGAAGGTAAUT GTUATUUUAUAGGGRGATTGTGGGUAUURGGGAGAUUXGUTGAGGGATGUTGUAG TGTAGAAGUTTUUUAAATUTARGUTGUTTUTUTTUUTUUTUAGTUUTUTUURGUTGU TGUUUTURGGTTUATGUUUTGTGGUTGATUUATUAURGGUTUTUUARGGUUTTUAU UTTGGGRGGGTTGGATGGUTG 228 AGUUATUUAAUURGUUUAAGGTGAAGGURGTGGAGAGURGGTGATGGATUAGUUA UAGGGUATGAAURGGAGGGUAGUAGRGGGAGAGGAUTGAGGAGGAAGAGAAGUA GRGTAGATTTGGGAAGUTTUTAUAUTGUAGUATUUUTUAGXGGGTUTUURGGGTGU UUAUAATRGUUUTGTGGGATGAUAGTTAUUTTUUUUAUTTUAUAGAAGGGAAGARG UUTUAGAGAGATGAUTUATRGGUUAGGTUUUATGGTGGGGUTGAUUURGTURGGT TGGTTUUAGUAUTUTUAGAGUUU 229 GURGURGUTTTTUUAGTUTTGUUUAAUURGGTATTTUTGRGUTTGUUTUAGUUAUUR GUAGGAGRGUAGGURGUUUTTRGTUUTUURGTUUTUTGRGUUUAUAGGAUUURGG GUUURGUUUAGTURGUAGGTUURGUAGGTUUUUURGGGXGTGTUTTUUTGGUUUTG RGAUUUURGGGAUAGRGUTGAGAAUARGRGGAAGGTGGGGAGARGRGRGGRGUTG GURGGGTUUUTGGRGURGTTUTRGRGGTGUAGUUTGTGUUTGGGAGTURGGURGTU UUAUUTUAGAAUUAGAGUAAA 230 TTTGUTUTGGTTUTGAGGTGGGARGGURGGAUTUUUAGGUAUAGGUTGUAURGRGA GAARGGRGUUAGGGAUURGGUUAGRGURGRGRGTUTUUUUAUUTTURGRGTGTTUT UAGRGUTGTUURGGGGGTRGUAGGGUUAGGAAGAUAXGUURGGGGGGAUUTGRGG GAUUTGRGGAUTGGGRGGGGUURGGGGTUUTGTGGGRGUAGAGGARGGGAGGARG AAGGGRGGUUTGRGUTUUTGRGGGTGGUTGAGGUAAGRGUAGAAATAURGGGTTG GGUAAGAUTGGAAAAGRGGRGGU 231 UUTGGGAUAGGUTUAATGGAGGUTGUAGGGUUATUAGURGAUTUUTARGUAGGUT UAGTUAGUAGUUUUUTGGUUAGUUUUAUUUUTGAUTGURGGUUTUAGAAUTGGGA GUTGUTTUUTGGUAGGGUURGUUTUTGUTGGGAGAURGGAXGGTGAGTUAGUUTTA AGUURGGUAUUAGAUUUUTUTGAGGATGGAGUAUUAGUTGGUTGUUUTGAGGUTG UAAAAUTTUTTUUUTRGTGGAGAUAGGGAGGUAUUTUAGAUAUTUAUUURGGAUT UUUTTGAAUAGGGAUAGGGAGGAA 232 TTUUTUUUTGTUUTTTGTTUAAGGGAGTURGGGGTGAGTGTUTGAGGTGUUTUUUTGT UTUUARGAGGGAAGAAGTTTTGUAGUUTUAGGGUAGUUAGUTUUTGUTUUATUUTU AGAGGGGTUTGGTGURGGGUTTAAGGUTGAUTUAUXGTURGGTUTUUUAGUAGAGG RGGGUUUTGUUAGGAAGUAGUTUUUAGTTUTGAGGURGGUAGTUAGGGGTGGGGU TGGUUAGGGGGUTGUTGAUTGAGUUTGRGTAGGAGTRGGUTGATGGUUUTGUAGUU TUUATTGAGUUTGTUUUAGG 233 AUAUTGTGGGGUAGGGAGGGGUATUTUTTGAGAAUAAAAGATUUATTTUTRGAUTT TUUAAAUTGGAGAGUTTUTTGAGAGAAAAGAGAGAGAUAGGTAUAGGTUUARGUU AUUUAUAUAUAGUUUTGTGUAUAUAGAURGGAUAUAGGXGTUUAUAGGUAAGTTR GUAGUTGUTUATTTTGTGAAGTGAATGUTGATTTGGGGGURGGGTGGGGTTRGTUTG TAUATRGTGUAUTGTUAGAUUUTTUUTGAAGGATTTTTGTTAUTGAAGTATUAGAAG GUUUTTGTTUTAAGGTGGTG 234 AUUAUUTTAGAAUAAGGGUUTTUTGATAUTTUAGTAAUAAAAATUUTTUAGGAAGG GTUTGAUAGTGUARGATGTAUAGARGAAUUUUAUURGGUUUUUAAATUAGUAUUU AUTTUAUAAAATGAGUAGUTGRGAAUTTGUUTGTGGAXGUUTGTGTURGGTUTGTG TGUAUAGGGUTGTGTGTGGGTGGRGTGGAUUTGTAUUTGTUTUTUTUTTTTUTUTUA AGAAGUTUTUUAGTTTGGAAAGTRGAGAAATGGATUTTTTGTTUTUAAGAGATGUU UUTUUUTGUUUUAUAGTGTG 235 AUUUARGGGGAUAGGGGTUAGAGTAATGGAGTGGAAATGGUAGGTTUAUAATTTTG GUTAUAGUTGUTUUUATUTUTAAGUAAUUUAGGUTURGGGTTGGAGGGTGGRGAUU UUAAGATGRGGUUTUAGURGURGGUXGTGTTTGTGUTUUAGUXGATGAAGXGAGTG UAAAGGGUTGTAUAAARGRGAGGUAUTGAAUAAAUAUTGAGRGTGURGTUUAGAT GTUURGGGGGAGGUTGAGGATUUAUAURGTGGGGAGTGUTUTGUUUUUATGGAGT GAUUTGGRGTURGUUUTUUARG 236 RGTGGAGGGRGGARGUUAGGTUAUTUUATGGGGGUAGAGUAUTUUUUARGGTGTG GATUUTUAGUUTUUUURGGGAUATUTGGARGGUARGUTUAGTGTTTGTTUAGTGUU TRGRGTTTGTAUAGUUUTTTGUAUTXGUTTUATXGGUTGGAGUAUAAAUAXGGURG GRGGUTGAGGURGUATUTTGGGGTRGUUAUUUTUUAAUURGGAGUUTGGGTTGUTT AGAGATGGGAGUAGUTGTAGUUAAAATTGTGAAUUTGUUATTTUUAUTUUATTAUT UTGAUUUUTGTUUURGTGGGT 237 RGAGGTGRGGUTGUUURGRGGUTTUUTRGGUTTUURGTUURGRGTGUTTTUUTGGA GTUUUTUUTTURGGAGGUUUTUUTGUUTUUARGTGTGUUUTTUTUUATGTUUAGUA TTRGGGRGUUTUTTGTUTTTUTTUTGTTUUUTGGUTTXGGRGTUUURGGGAGTGTGA UTUURGUAGRGGGGTGUAGUTTTUUTUTGGGATGAGTGAURGGAGGGAAUURGUUT TUURGGGUARGTRGUUAGUUTUTTUUTUTTUTTUUUTAGGUTATUAAGRGGAUTTAT GAUAAGAAGGRGGTGGAT 238 ATUUAURGUUTTUTTGTUATAAGTURGUTTGATAGUUTAGGGAAGAAGAGGAAGAG GUTGGRGARGTGUURGGGAAGGRGGGTTUUUTURGGTUAUTUATUUUAGAGGAAA GUTGUAUUURGUTGRGGGAGTUAUAUTUURGGGGARGUXGAAGUUAGGGAAUAGA AGAAAGAUAAGAGGRGUURGAATGUTGGAUATGGAGAAGGGUAUARGTGGAGGUA GGAGGGUUTURGGAAGGAGGGAUTUUAGGAAAGUARGRGGGARGGGAAGURGAGG AAGURGRGGGGUAGURGUAUUTRG 239 TGUAGTGTGTAUAGGAUTUUUTGAAAGGGUTUUUTGGGATGGAGGGTTTTTTGGGGG GGUUTGTGGTTUTTUTUUAGUATGAGTUAUAAAUUAUATUUTUUAUAGTUAGURGG ATUUAAAURGATTTGAURGAGATXGGUTUTTUAATGXGGTUTUURGGGGTGTUUUR GAGGATUTGGUTGGAUTTUUAGAGTAUUTGAGUAAGAUUAGUAAGTAUUTUAURG AUTRGGAATAUAUAGGTAGAUUUTGUUUTGTGGATUUAAGGUTAGGUATUUTGTGA GUTGATAGTTAGGTGGGUTGT 240 UAGUUUAUUTAAUTATUAGUTUAUAGGATGUUTAGUUTTGGATUUAUAGGGUAGG GTUTAUUTGTGTATTURGAGTRGGTGAGGTAUTTGUTGGTUTTGUTUAGGTAUTUTG GAAGTUUAGUUAGATUUTRGGGGAUAUUURGGGAGAUXGUATTGAAGAGUXGATU TRGGTUAAATRGGTTTGGATURGGUTGAUTGTGGAGGATGTGGTTTGTGAUTUATGU TGGAGAAGAAUUAUAGGUUUUUUUAAAAGUUUTUUATUUUAGGGAGUUUTTTUAG GGAGTUUTGTAUAUAUTGUAU 241 AGGAGUUTGTGAUUUAGAAATGGTAAGTAAGGTURGATTUTUAUUAAUAAAGUAG GUATGAUUTUAGAUAAGTUUUTAUUUTGUTUTGGGUUTUAGTTTUTUUTTTAGTGA GGAGGTGGGTGAGGGTUUTGTUUTUUTURGGGAAUTGGXGATTTGGGAAGGUAGAG AUATTUUUAGAATUXGURGGAGTUUTGAAAAUAUUUARGUUUTTTGTUUUAGUAAT UUTGAGAAAGGUUAUAUTGATAAAGUTGTGGGTGGUUAGATGAUAGUATTUTTGGG UUTUAGARGAAGTGGGAGGGG 242 UUUTUUUAUTTRGTUTGAGGUUUAAGAATGUTGTUATUTGGUUAUUUAUAGUTTTA TUAGTGTGGUUTTTUTUAGGATTGUTGGGAUAAAGGGRGTGGGTGTTTTUAGGAUTU RGGXGGATTUTGGGAATGTUTUTGUUTTUUUAAATXGUUAGTTUURGGAGGAGGAU AGGAUUUTUAUUUAUUTUUTUAUTAAAGGAGAAAUTGAGGUUUAGAGUAGGGTAG GGAUTTGTUTGAGGTUATGUUTGUTTTGTTGGTGAGAATRGGAUUTTAUTTAUUATT TUTGGGTUAUAGGUTUUTT 243 AGUUUTGGUTGAGTGUUUUUUAUTTUUUTGGUTRGAGTTUUUTUAUGAAAAAAUUT GGTGAUTUUTUUTGUAUAGAAUAAAGGUTGAGTGAGGUAUAGTGUUUAGGGGATG AGGAAGGUTGAGUURGGGAUUAGGUAGGAGGAAUUTGUXGTGUAUTUAUTUAGAU TUUTGUAGUAUURGGGGUAGGTGUTUUAUUAGRGGGUAUAGURGUTUAGURGUUT UUTUATUURGURGUAGUUAGTGGATUAUUAUAGUTGTUAGAGAGGUUUAUUAUTT GGUUAURGGGTUTARGUUTGUAGA 244 TUTGUAGGRGTAGAUURGGTGGUUAAGTGGTGGGUUTUTUTGAUAGUTGTGGTGAT UUAUTGGUTGRGGRGGGATGAGGAGGRGGUTGAGRGGUTGTGUURGUTGGTGGAG UAUUTGUUURGGGTGUTGUAGGAGTUTGAGTGAGTGUAXGGUAGGTTUUTUUTGUU TGGTUURGGGUTUAGUUTTUUTUATUUUUTGGGUAUTGTGUUTUAUTUAGUUTTTG TTUTGTGUAGGAGGAGTUAUUAUUTTTTTTUUTUAGGGAAUTRGAGUUAGGGAAGT GGGGGGUAUTUAGUUAGGGUT 245 UTUTGGGUTUTUTUUAUAGGGTTGAGGUUAGAGUTATTUTUAGAATUURGURGGAG GGGUUTTGUUTGGAGGAGGGUAUAARGAUAUTTAUTTGTUUUUATUAGUUGAUTG AGGGUTGGGGTTGGGUTGGGTUAUAUAGTTUAGTGUTXGUTUTAAGAGATGTTUUR GGAATAGUTGAGTUAUUTGGGUUAGGGGGTUUAUTGTGGAGAGGAGGAGGTGAGT GGGGTGGGGAGUAGGGUUUUAUUUTUUTUTUUAAGUTAAGGGUTTTTTUUTGGGTG GGUTGGGGUUAUAUUTAGGGUU 246 GUUUTAGGTGTGGUUUUAGUUUAUUUAGGAAAAAGUUUTTAGUTTGGAGAGGAGG GTGGGGUUUTGUTUUUUAUUUUAUTUAUUTUUTUUTUTUUAUAGTGGAUUUUUTG GUUUAGGTGAUTUAGUTATTURGGGAAUATUTUTTAGAGXGAGUAUTGAAUTGTGT GAUUUAGUUUAAUUUUAGUUUTGGGTUAGUTGATGGGGAUAAGTAAGTGTRGTTG TGUUUTUUTUUAGGUAAGGUUUTURGGRGGGATTUTGAGAATAGUTUTGGUUTUA AUUUTGTGGAGAGAGUUUAGAGU 247 RGUUUTGGUTUTGGGUTTTUAUUAURGUUTGGGGUUUTGUTTGGAUTUTGUAGUTG TGTUUUAAGGUTGRGUUUTAGATTTGTUTAUTUUTTUUUUTGUUUUUTUUUTGUTTT UTUURGGUUTUTGTAGTUTTUUTGUTUUTUUAUUTAXGTGGUTGUUTTGGGUUUUA TGUAGUTUUTUUUURGGGATGUUUUATGUTUTGTTUTGTGAUTGUUTTAUTUTTGAT UAUUTUTGATGGUTGUTUUAGTGUAGGUAGAAUUUUUAAAGTUUTUTGTTUTUTAU ATGTUUUUUTTTGUUAUU 248 GGTGGUAAAGGGGGAUATGTAGAGAAUAGAGGAUTTTGGGGGTTUTGUUTGUAUTG GAGUAGUUATUAGAGGTGATUAAGAGTAAGGUAGTUAUAGAAUAGAGUATGGGGU ATUURGGGGGAGGAGUTGUATGGGGUUUAAGGUAGUUAXGTAGGTGGAGGAGUAG GAAGAUTAUAGAGGURGGGAGAAAGUAGGGAGGGGGUAGGGGAAGGAGTAGAUA AATUTAGGGRGUAGUUTTGGGAUAUAGUTGUAGAGTUUAAGUAGGGUUUUAGGRG GTGGTGAAAGUUUAGAGUUAGGGRG 249 TTTUUTUUTUTUTTTUUTTUUTTUTUUAGTTUUTUUUTTTTUUTUUTTUAUTGTTTGA TTTTTAGUUUTUTGATTTTTTUTTUUTUTTUTUUAUTUTTTATTTUTTTTUATUUTUT UURGGTUUTTTTTTUTGUTTTGTUAUUTUUTTXGTTTTUTTUTUTUTUTGGUTGAUTU AGGGGAURGGAGGTGGGUUTATUTGGAGTGAGTGAGTAAGTGTGTTGGGAGGTGAG GGTGGAGGGUTGGAGGGGGGUAGTGATUTGGUUTGAGUUUUTUUAGTATTGUTUUA GUUUUAGURGUAG 250 UTGRGGUTGGGGUTGGAGUAATAUTGGAGGGGUTUAGGUUAGATUAUTGUUUUUU TUUAGUUUTUUAUUUTUAUUTUUUAAUAUAUTTAUTUAUTUAUTUUAGATAGGUU UAUUTURGGTUUUUTGAGTUAGUUAGAGAGAGAAGAAAAXGAAGGAGGTGAUAAA GUAGAAAAAAGGAURGGGAGGAGGATGAAAAGAAATAAAGAGTGGAGAAGAGGA AGAAAAAATUAGAGGGUTAAAAATUAAAUAGTGAAGGAGGAAAAGGGAGGAAUTG GAGAAGGAAGGAAAGAGAGGAGGAAA 251 UTATAUTUTUAGGUUUAGGUUAGGGGRGGUAGUTGUUUUUUTUAUTGUUUUARGU AUAAATUUUTGGTTTUAGTUUAAAURGUTAUTGTGAGUTUUAGATUTGGGTGGGGU URGGAGUUTUUTUATTAGUAUUAGGTGGGATGGUUTTGXGAAGATAAAGUTUTGTU TGGUUUUAGUUUAGGUTGTAGUUURGGGUUUTGUUUUAGGUAGUUTGUUUAGGAT GUTGTGUUAGTTTUTGAUUTTTGUUUAUTGUAGUUAGATGGGGUUATUTGTGGAGU TGGUUTTTTUTUUTTAGAATGA

252 TUATTUTAAGGAGAAAAGGUUAGUTUUAUAGATGGUUUUATUTGGUTGUAGTGGG UAAAGGTUAGAAAUTGGUAUAGUATUUTGGGUAGGUTGUUTGGGGUAGGGUURGG GGUTAUAGUUTGGGUTGGGGUUAGAUAGAGUTTTATUTTXGUAAGGUUATUUUAU UTGGTGUTAATGAGGAGGUTURGGGUUUUAUUUAGATUTGGAGUTUAUAGTAGRG GTTTGGAUTGAAAUUAGGGATTTGTGRGTGGGGUAGTGAGGGGGGUAGUTGURGUU UUTGGUUTGGGUUTGAGAGTATAG 253 ARGGGTGTUTGUTUUUAAGUTGGGUAUUUUTUUUUUAGGUTGTGGGAAURGUTGG GUUATTUTGAUUTRGAAUUAGAAATAGUUURGAUUUUUUTUTTTUTUUURGRGUUU UUAGURGGAURGUUUUURGGGAUUUUAGUUAAAUUAUAGXGTURGGUATAGGGU UTUTUUUTTATTGUAUAAURGUTAGGGGAGAUAGAGAGGATGGGGGTUURGGGAA UATGUTGGGGTRGUUAGAUTATGGGARGTAGGGGRGTAGUTUAUUTGTTGGAGAUA GGUURGUTUUTUAUTGGUTGAGTU 254 GAUTUAGUUAGTGAGGAGRGGGUUTGTUTUUAAUAGGTGAGUTARGUUUUTARGT UUUATAGTUTGGRGAUUUUAGUATGTTUURGGGAUUUUUATUUTUTUTGTUTUUUU TAGRGGTTGTGUAATAAGGGAGAGGUUUTATGURGGAXGUTGTGGTTTGGUTGGGG TUURGGGGGGRGGTURGGUTGGGGGRGRGGGGAGAAAGAGGGGGGTRGGGGUTAT TTUTGGTTRGAGGTUAGAATGGUUUAGRGGTTUUUAUAGUUTGGGGGAGGGGTGUU UAGUTTGGGAGUAGAUAUURGT 255 GUAGTAAAUAGTUUTATTGTAUAAATATATAGRGRGGGUTGGGRGGGGGRGGTUAA UUURGGTTUUUTGGUARGGGGAUAGGGRGRGUTGGGUURGGUTUTGUAGRGAGUR GGTGGGAGGGUUTAGUTGTGGUUUAGGRGGTGTTGAGUAXGGGURGGGGGRGTUA TAGURGGGGAGGGURGGGUAGRGAGRGGGTGGGRGAGGGGRGAGTUATRGTUTGU UURGUURGGAGGGGAUUURGGRGGGTGAGGGARGTGGGTGGAGGGAGARGTGGGG AGUTUAGTRGGAGTAGATGATGAA 256 TTUATUATUTAITTURGAUTGAGUTUUUUARGTUTUUUTUUAUUUARGTUUUTUAUU RGURGGGGTUUUUTURGGGRGGGGUAGARGATGAUTRGUUUUTRGUUUAUURGUT RGUTGUURGGUUUTUUURGGUTATGARGUUUURGGUUXGTGUTUAAUAURGUUTG GGUUAUAGUTAGGUUUTUUUAURGGUTRGUTGUAGAGURGGGUUUAGRGRGUUUT GTUUURGTGUUAGGGAAURGGGGTTGAURGUUUURGUUUAGUURGRGUTATATATT TGTAUAATAGGAUTGTTTAUTGU 257 AGTTATTTAATAUATGGUUUUAGTGGUAUTAALUTGTUAUTAAGUUTUATGTTUTU UATUUATAAAATGGAGAUUAUAATUATAUUTGUTGUAAAATUUAAAATTUAGAGGT TTUTAUAGRGTGAURGAUAUTGTGUUURGGAGAGTTTXGGUUUTUTUUTGGUTUTG GUUUUUTGGAAUARGTGATGUUUAGUUUAAAUAGTGUUAUAUUUTGUTUTAUAAT GUUTUAARGAGAGTUAUAAUUAAAGATTTTTGAGTUAGAGGAUAATAGAGGAGGT GGGAAUTGGGTAAAXGGAGAGT 258 UTUTUXGTTTAUUUAGTTUUUAUUTUUTUTATTGTUUTUTGAUTUAAAAATUTTTGG TTGTGAUTUTRGTTGAGGUATTGTAGAGUAGGGTGTGGUAUTGTTTGGGUTGGGUAT UARGTGTTUUAGGGGGUUAGAGUUAGGAGAGGGUXGAAAUTUTURGGGGUAUAGT GTRGGTUARGUTGTAGAAAUUTUTGAATTTTGGATTTTGUAGUAGGTATGATTGTGG TUTUUATTTTATGGATGGAGAAUATGAGGUTTAGTGAUAGGTTAGTGUUAUTGGGG UUATGTATTAAATAAUTG 259 GAGTTTXGGUUUTUTUUTGGUTUTGGUUUUUTGGAAUARGTGATGUUUAGUUUAAA UAGTGUUAUAUUUTGUTUTAUAATGUUTUAARGAGAGTUAUAAUUAAAGATTTTTG AGTUAGAGGAUAATAGAGGAGGTGGGAAUTGGGTAAAXGGAGAGTUUATGGUUTT TGGAGGTGGGGUAUAGUURGGAGTGAATGAGGGUUUAGAGTTTUUAGAGAAURGA ATATAGATUTGTGTGTGAAGUUTUUAGATATTUTAATGTTGAUAARGAAATUAAATT GAAAAAAAATAAAAATUAATA 260 ATTGATTTTTATTTTTTTTUAATTTGATTTRGTTGTUAAUATTAGAATATUTGGAGGUT TUAUAUAUAGATUTATATTRGGTTUTUTGGAAAUTUTGGGUUUTUATTUAUTURGG GUTGTGUUUUAUUTUUAAAGGUUATGGAUTUTUXGTTTAUUUAGTTUUUAUUTUUT UTATTGTUUTUTGAUTUAAAAATUTTTGGTTGTGAUTUTRGTTGAGGUATTGTAGAG UAGGGTGTGGUAUTGTTTGGGUTGGGUATUARGTGTTUUAGGGGGUUAGAGUUAGG AGAGGGUXGAAAUTUT 261 RGGGTGRGGAUURGUUAUUTGURGUAUUUTTUUUTTUUUAAUUUTGUUUTTTUUUU AUUUUUAUUUUAUTTUUUAUUUUUAAUUUURGUTRGGRGUUUUAUTUURGAUUUT GUUTGUURGGGUAUUTRGGGGRGTURGUTRGURGGUTTXGUUTUUAUTTGUUURGG UAGGRGRGRGTGGGUTRGGRGTUURGRGUTUUUTUUTRGAUTGTGRGGUTUURGRG UTGURGGGTTTUUTGTTUAAUAATATAAUUAGGGAGGUAURGGRGGAGAGRGURGG GUAGAAUTTUUTUURGGAUTG 262 UAGTURGGGAGGAAGTTUTGUURGGRGUTUTURGURGGTGUUTUUUTGGTTATATT GTTGAAUAGGAAAUURGGUAGRGRGGGAGURGUAUAGTRGAGGAGGGAGRGRGGG ARGURGAGUUUARGRGRGUUTGURGGGGUAAGTGGAGGXGAAGURGGRGAGRGGA RGUUURGAGGTGUURGGGUAGGUAGGGTRGGGAGTGGGGRGURGAGRGGGGGTTG GGGGTGGGAAGTGGGGTGGGGGTGGGGAAAGGGUAGGGTTGGGAAGGGAAGGGTG RGGUAGGTGGRGGGTURGUAUURG 263 GGUAAGGUAGTUTGGGRGURGTUTURGGTUTRGGGGUUTGRGGTRGGGGUAURGRG GTGURGRGTTTGAGURGGTUAGUTUUUTGRGGAAATTAUAGGGGRGUTRGGRGUTG RGGTRGRGUUUUURGGGGUAGRGUURGUTGGTTGGAGGXGTTTAAATTGAAAGUAG UTTTGGGGAGAGGGGGRGGARGRGGGURGURGAGUAAGGGGAGGGGGRGGUURGG UAUAGRGAUUUUATTGTUTGTGUURGURGAGGGGTGGAAUUTTGRGGTGAGUTRGG RGRGGRGUUUUUTUUURGAGU 264 GUTRGGGGAGGGGGRGURGRGURGAGUTUAURGUAAGGTTUUAUUUUTRGGRGGG UAUAGAUAATGGGGTRGUTGTGURGGGURGUUUUUTUUUUTTGUTRGGRGGUURGR GTURGUUUUUTUTUUUUAAAGUTGUTTTUAATTTAAAXGUUTUUAAUUAGRGGGRG UTGUUURGGGGGGRGRGAURGUAGRGURGAGRGUUUUTGTAATTTURGUAGGGAG UTGAURGGUTUAAARGRGGUAURGRGGTGUUURGAURGUAGGUUURGAGAURGGA GARGGRGUUUAGAUTGUUTTGUU 265 GGAGGGAGUUTGUAUTUTGGGUAGTGATGTGGAGTUAGAGATTTUUAAGTTUATGG TGUAAGTUTGTGGGAGAGUAGAAUTUAUTTTAUAAAATTGTTGAUAGURGGTGTTG TTAGAGARGGAAAGGGAUAAUUURGGUTUUTUTUUAGGXGTGGAGTUTGTGGGGAT GTGUTTUUAGAAAATGUAGGGTTAAGUAGGAGUTGUAGAGTAGAATUAAATGAUA ATGAUTUAUTGUTGTUAUTAAUAGGUTUTTTGTGGGGGUTGTAGGTGGGAGGRGAT ATGGURGGUAUUTTRGUAUAA 266 TTGTGRGAAGGTGURGGUUATATRGUUTUUUAUUTAUAGUUUUUAUAAAGAGUUT GTTAGTGAUAGUAGTGAGTUATTGTUATTTGATTUTAUTUTGUAGUTUUTGUTTAAU UUTGUATTTTUTGGAAGUAUATUUUUAUAGAUTUUAXGUUTGGAGAGGAGURGGG GTTGTUUUTTTURGTUTUTAAUAAUAURGGUTGTUAAUAATTTTGTAAAGTGAGTTU TGUTUTUUUAUAGAUTTGUAUUATGAAUTTGGAAATUTUTGAUTUUAUATUAUTGU UUAGAGTGUAGGUTUUUTUU 267 GTTUTGGTTRGGUAGAGTGGRGGUAATUTTGUUTUTUTUTUTAGAAUAUUTAAAGA AGUUAGTGAGTGAGUTGUTUATGUAUAURGGGGAGAUUTAUAGARGGATUUAGGA GGAGRGGGAGUTUATTGAUTGUAUAUTTUUAAUURGGXGTGATAGGAAAGTGAGG UUAUUTGTUUTAAGTGUURGGGGGUAGGGGGGTUUATGGAGGAGGGGGRGGGGGU AGGTGTUTGGAUAUAGGGATGUTGGTUTUAGGTGGUAUAGUTGGGGAGAAAAAAU UTATUUATTGUAAAAUATUATTAG 268 TAATGATGTTTTGUAATGGATAGGTTTTTTUTUUUUAGUTGTGUUAUUTGAGAUUAG UATUUUTGTGTUUAGAUAUUTGUUUURGUUUUUTUUTUUATGGAUUUUUUTGUUU URGGGUAUTTAGGAUAGGTGGUUTUAUTTTUUTATUAXGURGGGTTGGAAGTGTGU AGTUAATGAGUTUURGUTUUTUUTGGATURGTUTGTAGGTUTUUURGGTGTGUATG AGUAGUTUAUTUAUTGGUTTUTTTAGGTGTTUTAGAGAGAGAGGUAAGATTGURGU UAUTUTGURGAAUUAGAAUA 269 RGTGATUAGAGAUAGAAATUAGUTUUUUTUUTUUUTUAUTGAGUTTGTAGUUAUTT TAAGTATAAUUTGTGTUUTGTGUUAGTTUUAUUATAAATUAGUUUTGAGTTTTTATUR GGRGGUTTATTUTGUTGUUAAAAUUTTUAUAGTTGXGGGAATGGGUUAGGGAGAG AGUURGGAUTTTAUTURGGUTGTGGTGAUTUARGUUTTTGGGAAGGGUTGAGGTAT TTGTUUTTGGATGTGGGGATGUTGTGGUUTUTGGTTGGGAAUAUAGUUTRGTTTTGT UTGUTGGUTUTGGUTTUU 270 GGAAGUUAGAGUUAGUAGAUAAAARGAGGUTGTGTTUUUAAUUAGAGGUUAUAGU ATUUUUAUATUUAAGGAUAAATAUUTUAGUUUTTUUUAAAGGRGTGAGTUAUUAU AGURGGAGTAAAGTURGGGUTUTUTUUUTGGUUUATTUUXGUAAUTAATGAAGGTT TTGGUAGUAGAATAAGURGURGGATAGAAUTUAGGGUTGATTTATGGTGGAAUTGG UAUAGGAUAUAGGTTATAUTTAAAGTGGUTAUAAGUTUAGTGAGGGAGGAGGGGA GUTGATTTUTGTUTUTGATUARG 271 UAGTATGUATGTGTUUATTTAAGGUATUTGAGUUUTGGUUTTTGUTGTTUTTUUTTU UTTUTTimURGTRGGGTTGUTGAGUTUAAUATUUUAURGGGUTUUTGUTUUTTAGU TAGUAGTUAGTGUAGAGUTGUTGGGTUUTTUUGUUTXGUTTGGGUAGGUTTUTGTU AATGAGTUAUUAAGUAURGGGAAATAAGTGUAUAGGAAGGAGUAGGTGGUAAGAU UUTGTGGAGGTAGAGAUAGTTUUATTUAGTGAGTGAGUTGTGAUTGUAAATTTGGG AAGGTTUTGGGGGAAGUAA 272 TTGUTTUUUUUAGAAUUTTUUUAAATTTGUAGTUAUAGUTUAUTUAUTGAATGGAA UTGTUTUTAUUTUUAUAGGGTUTTGUUAUUTGUTUUUUUTGTGUAUTTATTTUURG GTGUTTGGTGAUTUATTGAUAGAAGUUTGUUUAAGXGAGGUAGAAGGAUUUAGUA GUTUTGUAUTGAUTGUTAGUTAAGGAGUAGGAGUURGGTGGGATGTTGAGUTUAGU AAUURGARGGAGAAAGAAGGAAGGAAGAAUAGUAAAGGUUAGGGUTUAGATGUU TTAAATGGAUAUATGUATAUTG 273 RGGURGRGGGGGGRGUUTGGAGGAGGGAAGUUTUTURGGAGGAGAAGAGUTGGGR GGURGURGTAGGAGGAAGRGGAAAGATAAGGGGUUUTRGGUTRGGRGGGGURGUR GGARGUUUAGGAGUUTUAATGGGGAUARGTRGGGTGGGGAXGGAGGUAGUTUUTG TURGGAUAGRGAAAUURGRGAGGUUUAGGAGAGRGGUAGUUAGRGRGGUAUAGUU RGGGAGUTGRGGUUUARGURGGAGUUTARGGAUATGGGUTRGGAAGGGAUAAAAA URGGGURGGAGTUAGRGUTGGAGUU 274 GGUTUUAGRGUTGAUTURGGUURGGTTTTTGTUUUTTURGAGUUUATGTURGTAGG UTURGGRGTGGGURGUAGUTUURGGGUTGTGURGRGUTGGUTGURGUTUTUUTGGG UUTRGRGGGTTTRGUTGTURGGAUAGGAGUTGUUTUXGTUUUUAUURGARGTGTUU UUATTGAGGUTUUTGGGRGTURGGRGGUUURGURGAGURGAGGGUUUUTTATUTTT URGUTTUUTUUTARGGRGGURGUUUAGUTUTTUTUUTURGGAGAGGUTTUUUTUUT UUAGGRGUUUUURGRGGURG 275 GUATUAUAUATUUUTUUUTGTUTUUUTGUTGUUAAUUAGTTUUAUUAUTGTUUAUU TUTGUUUUAATTUUAUUTUUUARGUUTGUTGUTGUAUUTTGGAUTTGTTTTUUTGAA ATTGUATGUUATUUAUTUTUUUTTUTAUTTUTGUTGXGTUUUTUTTGUUUTATUAGG AUUTGTGGAUTUAGGAUTUURGGGUTTTUTUUUUUATUTUTUTTUUURGTTGGGUU TUAUTAUUATTTUAGUUAUTTTUUTGGUAGUTTUAUTUUTGUUUUAAGAUUUUAGU UTTTUAUUUTUUTGGTTUT 276 AGAAUUAGGAGGGTGGAGGUTGGGGTUTTGGGGUAGGAGTGAAGUTGUUAGGAAA GTGGUTGAAATGGTAGTGAGGUUUAARGGGGAAGAGAGATGGGGGAGAAAGUURG GGAGTUUTGAGTUUAUAGGTUUTGATAGGGUAAGAGGGAXGUAGUAGAAGTAGAA GGGAGAGTGGATGGUATGUAATTTUAGGAAAAUAAGTUUAAGGTGUAGUAGUAGG RGTGGGAGGTGGAATTGGGGUAGAGGTGUAUAGTGGTGGAAUTGGTTGGUAGUAG GGAGAUAGGGAGGGATGTGTGATGU 277 GGTGGRGATGUTUTAGUUAUUTGUTTUTUTGTUUTUTTTUAUAUAAATGTATUUTGU TTUTTTUUAGATGTURGGUTTAATGGGAUTGGATTTATUTTUAAAAGTUUTGGTTTG UUTUTGATTGAAAAUUAGTGTGUTUUUUATGGTTAXGGARGGUTGTGUAGGTTTTTG TTTTGTTGAAGGGAATTGGUTUAUTUTGAGTUAGURGTGUAUURGGGUTGUTGATGT AGTUTUAGTGTGATGGTTAAAUTTTAAGTGTUAATTTGAUTGGGUTAAGGAATGUUA GAUATTATTTURGGG 278 UURGGAAATAATGTUTGGUATTUUTTAGUUUAGTUAAATTGAUAUTTAAAGTTTAA UUATUAUAUTGAGAUTAUATUAGUAGUURGGGTGUARGGUTGAUTUAGAGTGAGU UAATTUUUTTUAAUAAAAUAAAAAUUTGUAUAGURGTUXGTAAUUATGGGGAGUA UAUTGGTTTTUAATUAGAGGUAAAUUAGGAUTTTTGAAGATAAATUUAGTUUUATT AAGURGGAUATUTGGAAAGAAGUAGGATAUATTTGTGTGAAAGAGGAUAGAGAAG UAGGTGGUTAGAGUATRGUUAUU 279 GGTTTTGGGTGTGGAUATUUUTGGAGGGUTGTTTTAGTGUUUAUAUUAATGUUUTAG TTAAAGAAUUAUUUTGTUUUUTTAGUUTTUTGUAGGAUAGGTGGGAAAGGGURGG GTGTUTGGTUUTGUTGUUAGGGGAUAGTGUAGGTGTGAUXGTURGGGUAGAGATGA GTUAUUUTUUAUAUTGTUTTGUTGUURGTUTUUARGUUTAGTTTTAGUTRGTGTGGT UAAGAAGGGGRGATTUUTUAUUTAGAAUAUATGGGTUAUAAATGUTAUUTTTGAAA ATGGAAAUAAAAATAAUUUA 280 TGGGTTATTTTTGTTTUUATTTTUAAAGGTAGUAUUAAATGGATTGGTGTGAUUU AGGAATRGUUUUTTUTTGAUUAUARGAGUTAAAAUTAGGRGTGGAGARGGGUAGU AAGAUAGTGTGGAGGGTGAUTUATUTUTGUURGGAXGGTUAUAUUTGUAUTGTUUU UTGGUAGUAGGAUUAGAUAUURGGUUUTTTUUUAUUTGTUUTGUAGAAGGUTAAG GGGAUAGGGTGGTTUTTTAAUTAGGGUATTGGTGTGGGUAUTAAAAUAGUUUTUUA GGATGTUUAUAUUUAAAAUU 281 UAGAAUUTGAGRGATGAAGTGARGGGATTTAGTUAGGUUTATGAAGAGTUAATGGU AUTTGUUTUUUATAATUUTTUUAGTUUUATTGGUUAAUURGTUTGTUUUTRGRGTG ATUTTTTGGATUTGAAGTGGTGTTTUAGGAUURGGAGXGTGGUUTGUAUTGUUTTG TTUTGTTTGTTTGTGUAURGGATTUATRGTGAUTUATUUTGAGTUATUUAGGUAGTA TGGAAGAAUTTTGGAGTTATTTTAAAUUUTTTGGUTUAGAAUUUUATTTGGAGGAT ATTAAUATGUAAGATAA 282 TTATUTTGUATGTTAATTUTAGAAGAAATGGGGTTUTGAGUUAAAGGGTTTAAAATA AUTUUAAAGTTUTTUUATAUTGUUTGGATGAUTUAGGATGAGTUARGATGAATURG GTGUAUAAAUAAAUAGAAUAAGGUAGTGUAGGUUAXGUTURGGGTUUTGAAAUAU UAUTTUAGATUUAAAAAGATUARGRGAGGGAUAGARGGGTTGGUUAATGGGAUTG GAAGGATTATGGGAGGUAAGTGUUATTGAUTUTTUATAGGUUTGAUTAAATUURGT UAUTTUATRGUTUAGGTTUTG 283 GTUUUTTGGUAUUAGGAUATUAUUUTUUUAUUTUTUUUAGAUUUTTUTUUTTGAUU TUTTTAGAGUAGUUATUUTTGGAGTTGUTUAARGUUUTGRXXRGGAAGGTTGAAUR UUAUAGUTTGGUTUATUTAUTTURGGGTTAGUTUAAXGUUUTUTTUTTTTUUUG TGAAUUAUAGUTTGGUTUATUTAUTURGGGTTAGUTUAARGUAUTUTTUTUTUTU UUTUTGAAUUARGGUTTGGUTUATUTAUTTUTGGGTTAATTTAGGUTTTUTUUAUAG ATAGTUTGAAAAGGGA 284 TUUUTTTTUAGAUTATUTGTGGAGAAAGUUTAAATTAAUUUAGAAGTAGATGAGUU AAGURGTGGTTUAGAGGGAGAAGAGAAGAGTGRGTTGAGUTAAUURGGAAGTAGA TGAGUUAAGUTGTGGTTUAGAGGGAGAAAAGAAGAGGGXGTTGAGUTAAUURGGA AGTAGATGAGUUAAGUTGTGGTTUAGAGGGAGAAGAGAAGAGGGRGTTGAGUAAU TUUAAGGATGGUTGUTUTAAAGAGGTUAAGGAGAAGGGTUTGGGAGAGGTGGGAG GGTGATGTUUTGGTGUUAAGGGAU 285 UTGAGTUAAUAAGGUTGAUAAGGUTGTGTTUTGGATGUAGGUURGGUAGATGTTTG AGGGGGAGGTGGUUAGUUTGGAGGUUUTUAGGAGUARGGGUUTGGTGRGGGTGUR GAGGUUUATGAAGGTUATRGAUUTGURGGGAGGTGGGGUXGUUTTTGTGATGGAGU ATTTGAAGATGAAGAGUTTGAGUAGGTGAGTGTGTGTGAGAUUUATATGRGUAUAT GTGTAUAGGUAGAGAGAGAUTUAGAGAUAAAUAGAGAGAGAUAGAGAAAGGGAT AGAGATGGGGAGGGAGAUAGAAA 286 TTTUTGTUTUUUTUUUUATUTUTATUUUTTTUTUTGTUTUTUTUTGTTTGTUTUTGAG TUTUTUTUTGUUTGTAUAUATGTGRGUATATGGGTUTUAUAUAUAUTUAUUTGUTU AAGUTUTTUATUTTUAAATGUTUUATUAUAAAGGXGGUUUUAUUTUURGGUAGGTR GATGAUUTTUATGGGUUTRGGUAUURGUAUUAGGUURGTGUTUUTGAGGGUUTUU AGGUTGGUUAUUTUUUUUTUAAAUATUTGURGGGUUTGUATUUAGAAUAUAGUUT TGTUAGUUTTGTTGAUTUAG 287 TTRGTGUAUTUTGRGGURGRGGRGGUAGUAGURGRGGRGGRGGUUAGUTUUURGGT UTARGTGUUUAUUAUURGRGTGGGTTUUATGUTGUURGGUUTAURGTAUUAUUTGU AGGGGTRGGGUAGTGGGUUAGUUAAUUARGRGGGRGGXGRGGGRGRGUAUUURGG UTGGUUTUAGGUUTRGGURGAUAGUUUTUUATARGGUAGRGGAGGRGGRGRGGUT GGRGGRGGGGURGRGGGGUUTGGRGGRGUTGGUTUAGURGRGGRGUARGTUTRGGR GRGUTTUUUUTAUTUTUUUAGU

288 GUTGGGAGAGTAGGGGAAGRGRGURGAGARGTGRGURGRGGUTGAGUUAGRGURG UUAGGUUURGRGGUUURGURGUUAGURGRGURGUUTURGUTGURGTATGGAGGGU TGTRGGURGAGGUUTGAGGUUAGURGGGGTGRGRGUURGXGURGUURGRGTGGTTG GUTGGUUUAUTGUURGAUUUUTGUAGGTGGTARGGTAGGURGGGUAGUATGGAAU UUARGRGGGTGGTGGGUARGTAGAURGGGGAGUTGGURGURGURGRGGUTGUTGU RGURGRGGURGUAGAGTGUARGAA 289 TUTTTGTGTGAGTUATGTUTTATATUUAAUAAGTAUTUAAAAAAAGATTTTTTTTTTT TTTTTTTAAGATGGAGTGTRGUTUTGTUAUUUAGGUTGGAGTGUAGTGGUATGATUT TGGUTUAUTGUAAUUUTGUUTUURGGGTTUAAGXGATTUTTUTGUUTUAGGUTUU TGAGTAGUTGGAATTAUAGGUATGUUUUAUUAUAUURGGUTAATTTTTATATGTAA TAGAAAUAAGGTTTUAUUATGTTGGUUAGAUAGGTUTTGAAUTUUTGAUUTUAGGT GATUUAUUUAUUTRGGU 290 GURGAGGTGGGTGGATUAUUTGAGGTUAGGAGTTUAAGAUUTGTUTGGUUAAUATG GTGAAAUUTTGTTTUTATTAUATATAAAAATTAGURGGGTGTGGTGGGGUATGUUTG TAATTUUAGUTAUTUAGGAGUUTGAGGUAGAAGAATXGUTTGAAUURGGGAGGUA GAGGTTGUAGTGAGUUAAGATUATGUUAUTGUAUTUUAGUUTGGGTGAUAGAGRG AUAUTUUATUTTAAAAAAAAAAAAAAAAAATUTTTTTTTGAGTAUTTGTTGGATATA AGAUATGAUTUAUAUAAAGA 291 AUUAUUUUUTGAUUUUTUATGAUTUAUUUAGUTUUTAAGTGUUUUTGGGUAUUUA GTTUTTTGTGGUATGGGURGGTGUAAGTTTUTATATGAGAGUUAGAGAGAUAGGGA GGGAGGUURGGGUTUUTGGUUTTTTGGGAAAAGATGUUXGTUTUAGAUUAGUAAA AGGAGGUAGUTGUTTTAGGAGUURGGGAAAATGUUATUAUTGATAGTATTATTATT ATTTTUUUATTTTUUUTTTGTGTTTTTAAAATGAAAAGTTUAGATUUATGGGGTAGG GTAGAGTGGGUUTGGAGGGAG 292 TUUUTUUAGGUUUAUTUTAUUUTAUUUUATGGATUTGAAUTTTTUATTTTAAAAAU AUAAAGGGAAAATGGGAAAATAATAATAATAUTATUAGTGATGGUATTTTUURGGG UTUUTAAAGUAGUTGUUTUUTTTTGUTGGTUTGAGAXGGGUATUTTTTUUUAAAAG GUUAGGAGUURGGGUUUUTUUUTGTUTUTUTGGUTUTUATATAGAAAUTTGUAU RGGUUUATGUUAUAAAGAAUTGGGTGUUUAGGGGUAUTTAGGAGUTGGGTGAGTU ATGAGGGGTUAGGGGGTGGTT 293 GUAGUARGUAGUUUUUAGGGGUUUTAAUTUAUUUUUTUTTUUUTUAUAGGGUTTU UUTGURGTUUAGTGTTGGGTGAGAAAGGTGGAGGGGAUATGTAGUUURGGATGGAG GTGUAGUAUUAARGAGAGAGUTURGGUUTGTGGGAGGGAXGUTUAGGUTTAGGTU AAAGUUAGGAGUTURGGGAAAUUTGGGTTUAGURGUUARGUUUUARGGAGGGGAU AUAUUUTTUUUTGUUTGATGGUAGGGUUUATGGTAGAUAAAAUUUATGAUUTUAU UTUTUUTGGUTUUAGGGUTUAGUU 294 GGUTGAGUUUTGGAGUUAGGAGAGGTGAGGTUATGGGTTTTGTUTAUUATGGGUUU TGUUATUAGGUAGGGAAGGGTGTGTUUUUTURGTGGGGRGTGGRGGUTGAAUUUA GGTTTUURGGAGUTUUTGGUTTTGAUUTAAGUUTGAGXGTUUUTUUUAUAGGURGG AGUTUTUTRGTTGGTGUTGUAUUTUUATURGGGGUTAUATGTUUUUTUUAUUTTTUT UAUUUAAUAUTGGARGGUAGGGAAGUUUTGTGAGGGAAGAGGGGGTGAGTTAGGG UUUUTGGGGGUTGRGTGUTGU 295 ATTTUTTTUTAUUTGTUATTGAAGTGAATUATUAGTATAAGTAGRGAGUTGGGRGUA TTUUTTUTUAGTTGTGTTAAAAUTTGUTGGTATTUUUURGGTATUAGUAGAGGTGTG TARGGGUAUTGUTTTAAAAUTGGGAAGGAGGAAGAXGAGGUUAGGGAGURGGAGG GTUAUUAAGGTAGATTTUUAGUAGRGUTAGTUUAGUTGAAUAUTTTUUAGUUTTGT TTTTUAGUAGUTTTGAGGAAAAGTATAGGTAAGAAUAAAGAUAUUAUTGTATGTTT GUTATATGAATGUATAAUA 296 GTTATGUATTUATATAGUAAAUATAUAGTGGTGTUTTTGTTUTTAUUTATAUTTTTUU TUAAAGUTGUTGAAAAAUAAGGUTGGAAAGTGTTUAGUTGGAUTAGRGUTGUTGGA AATUTAUUUTGGTGAUUUTURGGUTUUUTGGUUTXGTUTGAATTUUUGGUUATTA AAGUAGTGUURGTAUAUAUUTUTGUTGATAURGGGGGAATAUUAGUAAGTTTTAAU AUAAUTGAGAAGGAATGRGUUUAGUTRGUTAUTTATAUTGATGATTUAUTTUAATG AUAGGTAGAAAGAAATG 297 ATTGGTUTGGTUUTUTTTUTAAUAUUTUUUAUURGGGATGUAGUUAAGAGTGGUTG UAGUUTAATTTTUTAUATGTAAAUAATGAUUTUAGTGATGUUUARGGGGUUUUTUT UTGGUUTTUTUUUUUTGGGAAAAGAUTGAGTTUTRGAXGGGUATUUUUTUUUUUTU RGGAAUUAAGGGUTUTGGGATGTTGAUAGUUUURGUUAUUTUTGAGAAGGGUAGG URGTGGAAAAUUATUTUUTUUUTTUUTTUUUUUTUTGUTUTUUTAGUTGGGGUUT UTGUAUAATGUAGUTGGGUUA 298 TGGUUUAGUTGUATTGTGUAGAGGUUUUAGUTAGGAAAGGUAGAGGGGGAAGGAA GGGAGGAGATGGTTTTUUARGGUUTGUUUTTUTUAGAGGTGGRGGGGGUTGTUAAU ATUUUAGAGUUUTTGGTTURGGAGGGGGAGGGGATGUUXGTRGAGAAUTUAGTUTT TTUUUAGGGGGAGAAGGUUAGAGAGGGGUUURGTGGGUATUAUTGAGGTUATTGT TTAUATGTAGAAAATTAGGUTGUAGUUAUTUTTGGUTGUATUURGGGTGGGAGGTG TTAGAAAGAGGAUUAGAUUAAT 299 TTGUUUTUATUTUUAGGUTTTGGAGGAGGGTAGGTGUUTGGUUAGUAGAGTGGUUA UTGUTUAUTGGUUUAGAGGAAGUAAGGUUAUUAGUUTGATUUUAUTTUTUUUTUR GGUUUATUTTUAUTUUUUTUTUUTUAAUUAUAAGUUUXGUUAAAATAGAGAUUUU RGGUTTTGUTUUUUTGUTGUAGGAAGGGAGAGUUAURGUUAGAUAUTGUUTGUUT GGTUUTUUTGTTUTGATUTUAUURGGTGUTTGGAATUAAAGAGGAUUTGGUTTUUU TUTRGGGATARGTGATTTTUTTT 300 AAGAAAATUARGTATUURGAGAGGGAAGUUAGGTUUTUTTTGATTUUAAGUAURGG GTGAGATUAGAAUAGGAGGAUUAGGUAGGUAGTGTUTGGRGGTGGUTUTUUUTTU UTGUAGUAGGGGAGUAAAGURGGGGGTUTUTATTTTGGXGGGGUTTGTGGTTGAGG AGAGGGGAGTGAAGATGGGURGGAGGGAGAAGTGGGATUAGGUTGGTGGUUTTGU TTUUTUTGGGUUAGTGAGUAGTGGUUAUTUTGUTGGUUAGGUAUUTAUUUTUUTUU AAAGUUTGGAGATGAGGGUAAG 301 GUUUAGATUAGGUAGRGGGGTRGUUUTUTUUAGGAUTUTUAAGGUAGUTAAGGUT GGAGGRGURGGRGAGUUTGGAGAGGGAGGAGTTUAUTAAATTGTGTTGGATGGAAG GRGTRGAGGAURGGAGGAATTAATURGATGTGGGGAAGGXGGARGGGGUTARGAG GAAAAAAGAGGGGGUAATGTAUAUTUAGUUTTTTUATUAUTRGGRGGGGAGATGGA TGGTTTTURGGAURGGGRGTUUUAGRGUUURGGTTAGUTATAGGGAGARGTUAGAG RGUTUTGGTURGRGATAGAAGA 302 TUTTUTATRGRGGAUUAGAGRGUTUTGARGTUTUUUTATAGUTAAURGGGGRGUTG GGARGUURGGTURGGAAAAUUATUUATUTUUURGURGAGTGATGAAAAGGUTGAG TGTAUATTGUUUUUTUTTTTTTUUTRGTAGUUURGTUXGUUTTUUUUAUATRGGATT AATTUUTURGGTUUTRGARGUUTTUUATUUAAUAUAATTTAGTGAAUTUUTUUUTUT UUAGGUTRGURGGRGUUTUUAGUUTTAGUTGUUTTGAGAGTUUTGGAGAGGGRGAU UURGUTGUUTGATUTGGGU 303 ATTTGGUTTGATUTTATTTTTAATATTTTTTAUAUTTTUTUTUTAAAGAAAA RGAGTGAATATRGTGATGGGTGUAGTTATGUTGAATAATTGGATGGGAGGARGTGU UAGGRGATUTUUAGUUUUTGGGAGURGGARGUUUAXGUTTTUUUTUTGUUTRGTTUT UAUAGAUAUATTTGTGGGGTGATTAAUTUAGGAATTUATGUTGUTUAAAGTAAUTA UAGTGGTGAGTGTTTTGAURGGTTTGATGTAGAAATUAAGGAAAAUAUUAGAAAAA TUAGGGGRGGAGGUUUAA 304 TTGGGUUTURGUUUUUGATTTTTUTGGTGTTTTUUTTGATTTUTAUATUAATTGT AAAAUAUTUAUUAUTGTAGTTAUTTTGAGUAGUATGAATTUUTGAGTTAATUAUUU UAUAAATGTGTUTGTGAGAARGAGGUAGAGGGAGGXGTGGGRGTURGGUTUUUAG GGGUTGGAGATRGUUTGGUARGTUUTUUUATUUAATTATTUAGUATAAUTGUAUUU ATUARGATATTUAUTRGUUTTTTTTTTUTTTAGAGAGAAAGTGTAAAAAATATTAAA AATAAGATUAAGUUAAAT 305 TGAUTTTTTUATTTUTUTUAAGATGATUATTAGGAGTGGTTTUAAUAAAAUTGAAUA UAGAATTTTGAGGGUUUUAATUATGAUTUAAUUAGAGUUUTUUUTGAATTUTTUAT GAGTUAGUURGGUUUTUUUUAUTGAUTTUAUUUTAGXGGGUAUUTGTUTTTUTTUT TUTTTTATUAUTTTTTGUTTUTUTTTTGGTTTUUAGUTUTGGTTTTUTUUGAATA UAUUTTUUAATTUTTUURGGUUUUUTUAGGGAAAUUUAGAGGUAAATTTGAGTGUA GGGAGRGGGGGUTTRGU 306 GRGAAGUUUURGUTUTUTGUAUTUAAATTTGUUTUTGGGTTTUUUTGAGGGGGURG GGAAGAATTGGAAGGTGTTGGGTUTGAATTUAGTUAGAGUTGGAAAUUAAAAGAGA AGUAAAAAGTGATAAAAGAAGAAGAAAGAUAGGTGUUXGUTAGGGTGAAGTUAGT GGGGAGGGURGGGUTGAUTUATGAAGAATTUAGGGAGGGUTUTGGTTGAGTUATGA TTGGGGUUUTUAAAATTUTGTGTTUAGTTTTGTTGAAAUUAUTUUTAATGATUATUT TGAGAGAAATGAAAAAGTUA 307 GGTGTUAGGAGTGGUUUAGGAGAGUAUUURGTTUUURGGUURGUAGGTGGTGTTTG UTGGUTUUAGUAGGGUUAGGAGGUUAUUTGUAGUUTGGTGUTUUAGAUTGATGTU AUURGGGURGAGTGUTGTGUUTURGGUAAUATTGAUAUXGUUTGGTUUAAUUTUA UUUAUURGGGGAAUAAGATUAAUUTUUTRGGUTTTTTTGGGUUTTGTUUAUTGUUTT UUUTGUAAAGGTGAGAUUTUAGGUUAGAAGUAGGGUAGARGTUTUAGUTUAGGAU UAGUUAUAAAUAGTUATGGTGGT 308 AUUAUUATGAUTGTTTGTGGUTGGTUUTGAGUTGAGARGTUTGUUUTGUTTUTGGU UTGAGGTUTUAUUTTTGUAGGGAAGGUAGTGGAUAAGGUUUAAGAAGURGAGGAG GTTGATUTTGTTUUURGGGTGGGTGAGGTTGGAUUAGGXGGTGTUAATGTTGURGG AGGUAUAGUAUTRGGUURGGGTGAUATUAGTUTGGAGUAUUAGGUTGUAGGTGGU UTUUTGGUUUTGUTGGAGUUAGUAAAUAUUAUUTGRGGGURGGGGAARGGGGTGU TUTUUTGGGUUAUTUUTGAUAUU 309 GUAGUUUTUTTUAUUTGUUTGGTGAUTUAUTAUAAGUUUTGGGGGAAGGAATGGU AGTGGUUUTUTTUAUUTTTAUTGUUTUTGRGGUUAUAATGGGUAGTTGAUATAAUU AUUTGUAGGUUURGGGAGUUATXGGGGUUTUTTGAUAXGTGUTUATTAGTGGUTTU TGAGGAGRGUUTGUUUUAUUTGUUUUAXGTGUUUUUAXGTUTGGUUAUTUUAGGG TUUATTAGRGUTAATRGGUAAATGUUTGTGUTUTUATUTAURGGGAAAAUATUTUU UTTUTUUAGAGRGGAGGUUAGU 310 UTGGUUTURGUTUTGGAGAAGGGAGATGTTTTUURGGTAGATGAGAGUAUAGGUAT TTGURGATTAGRGUTAATGGAUUUTGGAGTGGUUAGAXGTGGGGGUAXGTGGGGUA GGTGGGGUAGGRGUTUUTUAGAAGUUAUTAATGAGUAXGTGTUAAGAGGUUUXGA TGGUTUURGGGGUUTGUAGGTGGTTATGTUAAUTGUUUATTGTGGURGUAGAGGUA GTAAAGGTGAAGAGGGUUAUTGUUATTUUTTUUUUUAGGGUTTGTAGTGAGTUAUU AGGUAGGTGAAGAGGGUTGUT 311 GTGGUUUTUTTUAUUTTTAUTGUUTUTGRGGUUAUAATGGGUAGTTGAUATAAUUA UUTGUAGGUUURGGGAGUUATRGGGGUUTUTTGAUAXGTGUTUATTAGTGGUTTUT GAGGAGRGUUTGUUUUAUUTGUUUUAXGTGUUUUUAXGTUTGGUUAUTUUAGGGT UUATTAGRGUTAATRGGUAAATGUUTGTGUTUTUATUTAURGGGAAAAUATUTUUU TTUTUUAGAGRGGAGGUUAGUUTAAAAAUUAGGUURGUAGUUTURGAGGUTUTGA AAAUUAAGRGGUTGTTUTGGTU 312 AUUAGAAUAGURGUTTGGTTTTUAGAGUUTRGGAGGUTGRGGGUUTGGTTTTTAGG UTGGUUTURGUTUTGGAGAAGGGAGATGTTTTUURGGTAGATGAGAGUAUAGGUAT TTGURGATTAGRGUTAATGGAUUUTGGAGTGGUUAGAXGTGGGGGUAXGTGGGGUA GGTGGGGUAGGRGUTUUTUAGAAGUUAUTAATGAGUAXGTGTUAAGAGGUUURGA TGGUTUURGGGGUUTGUAGGTGGTTATGTUAAUTGUUUATTGTGGURGUAGAGGUA GTAAAGGTGAAGAGGGUUAUT 313 ATGGGUUUTGGGGURGURGUUTUAGTGTUTTUTGGTGUTGUAGURGGGUAGGGURG AAUUUTGGRGUAUAGUTTUUTGUTGAGTUTUUUTUTUTAAGGUTGTUTGTGGGRGG UTUTGURGGUUUUTUUTGUAUUTGUUUAGGUUUTGGGXGGAGGUTUUTUUTUURG GGGGGGUTGTGGUUTUAGUAUAGAUUAGGGGAUAGAAGGTGGUTUTTUTTGGUUTT GGUTGGGTGTGAAUUAAAGAUTTUUTGTAAGAAATUUUUUTUTUUUTUTUUUTUUT TRGUTUUUTUATUTUTUTUUU 314 GGGAGAGAGATGAGGGAGRGAAGGAGGGAGAGGGAGAGGGGGATTTUTTAUAGGA AGTUTTTGGTTUAUAUUUAGUUAAGGUUAAGAAGAGUUAUUTTUTGTUUUUTGGTU TGTGUTGAGGUUAUAGUUUUUURGGGAGGAGGAGUUTUXGUUUAGGGUUTGGGUA GGTGUAGGAGGGGURGGUAGAGURGUUUAUAGAUAGUUTTAGAGAGGGAGAUTUA GUAGGAAGUTGTGRGUUAGGGTTRGGUUUTGUURGGUTGUAGUAUUAGAAGAUAU TGAGGRGGRGGUUUUAGGGUUUAT 315 UAUTGGAUUATUUAUAUAAUTTTTGAGGATUAGTGGAAATGAAAAUARGGTGUUUR GGUAUAAAAUATATTTUATAGUTTGGGTTAGGUAAUAGUAAAGUATUARGUTGAGR GURGGGAUUTTUTGAGTGUAGGXGGTGGGXGAAGUUURGAGTUAUAUAUAUUUAR GAXGURGGUUUTGUTUUUAUAGRGGUUUTUTGGGGTAGRGAUTGGTATTAUUTGUA TTTUARGAGGGAGGAAAUTGAGGUARGAAUTGTTUAGAAGUTGUUUTGAGGTUAUU AAGTGAGUTAGGAAGAGGRGT 316 RGUUTUTTUUTAGUTUAUTTGGTGAUUTUAGGGUAOUTTUTGAAUAGTTRGTGUUT UAGTTTUUTUUUTRGTGAAATGUAGGTAATAUUAGTRGUTAUUUUAGAGGGURGUT GTGGGAGUAGGGURGGXGTRGTGGGTGTGTGTGAUTRGGGGUTTXGUUUAUXGUUT GUAUTUAGAAGGTUURGGRGUTUAGRGTGATGUTTTGUTGTTGUUTAAUUUAAGUT ATGAAATATGTTTTGTGURGGGGUAURGTGTTTTUATTTUUAUTGATUUTUAAAAGT TGTGTGGATGGTUUAGTGT 317 UTUUAGTGTGUUTUAGTTGGTTTATUTGTAAAAATGGGGUUAGGUUARGAUTGGTG TTUUUTTTAUAGAGAAGUAUTUUAGGUAGGGGTGGGTGGGGGTGGAAUTRGTTUTU AATGGUUUURGGGAUAGUUUTGUAGUUAURGGTGAUTXGGGTTXGTUTGRGGATUT TTUURGGUUTUUAUTUUATTUAGGGAUAGUUUTGUAATGGGGUTUUUTUUUAAAA AAARGUATGGUUTTUUTGTUUUUUAAAAUUAGUTTAARGGUAGUUATTUUUTUUUT UUTURGGGGGUTGAAAAAUUA 318 GGTTTTTUAGUUUURGGAGGAGGGAGGGAATGGUTGURGTTAAGUTGGTTTTGGGG GAUAGGAAGGUUATGRGTTTTTTTGGGAGGGAGUUUUATTGUAGGGUTGTUUUTGA ATGGAGTGGAGGURGGGAAAGATURGUAGAXGAAUUXGAGTUAURGGTGGUTGUA GGGUTGTUURGGGGGUUATTGAGAARGAGTTTTUAUUUUUAUUUAUUUUTGUUTGG AGTGUTTUTUTGTAAAGGGAAUAUUAGTRGTGGUUTGGUUUUATTTTTAUAGATAA AUUAAUTGAGGUAUAUTGGAGG 319 UAUTUARGGGUTAGUTURGTUAGGTGTTGARGGATGTUAUTUAGGTGTGAGUTUTG UAUUTGAGUTUUUUUUTGUAUAUAGGUAGUUAUAAUUAGTUAGTGUAGAGGTGAG UTTTGTGGUUAGTGAGGAGURGGTGAGTUAAUUTUUTUUXGUUTARGGGUUUTGAG ARGURGGUTURGTGAGUTTGRGGGGTRGAGGGRGUUTATATTAAGUUAAGGUTGAG GUAGTGAUAUAUUUTUTTATGGGUUTGUTUTRGUTTUUTGUTTUATTGTUUTGGTUT UTUUUTUTRGTATGGAGGATUA 320 TGATUUTUUATARGAGAGGGAGAGAUUAGGAUAATGAAGUAGGGAGRGAGAGUAG GUUUATAAGAGGGTGTGTUAUTGUUTUAGUUTTGGUTTAATATAGGRGUUUTRGAU UURGUAAGUTUARGGAGURGGRGTUTUAGGGUURGTAGGXGGGAGGAGGTTGAUT UAURGGUTUUTUAUTGGUUAUAGGUTUAUUTUTGUAUTGAUTGGTTGTGGUTGUUT GTGTGUAGGGGGGAGUTUAGGTGUAGAGUTUAUAUUTGAGTGAUATURGTUAAUA UUTGARGGAGUTAGUURGTGAGTG 321 UUAGGUTGUUTGGGTTTTGGTUTUUAUUATGUTAGUTTGGTGTURGAUUTGTGTTGAGAUUU TUUUTGUUTUTGGUURGGGTGTUUUATUUAAGUAATGGAUAGGTTGGAAUAGGXGTTXGTA GGGAAXGGGUTGAAXGUURGRGGUTUUXGXGATGTUTXGXGATAUTAUUTUUUTXGUUUUX GUTUAUTTAAGGAURGGAAGTAGUAAAGUURGURGTRGRGUUUUURGUUURGRGTUTUUUT GGTAAUUAGUUTUTUUUUTTUUUTRGUUUATAAGGAGUAAGRGGUAUAAATRGGG 322 UURGATTTGTGURGUTTGUTUUTTATGGGRGAGGGAAGGGGAGAGGUTGGTTAUUAGGGAGA RGRGGGGRGGGGGGRGRGARGGRGGGUTTTGUTAUTTURGGTUUTTAAGTGAGXGGGGGXG AGGGAGGTAGTATXGXGAGAUATXGXGGGAGURGRGGGXGTTUAGUUXGTTUUUTAXGAAX GUUTGTTUUAAUUTGTUUATTGUTTGGATGGGAUAUURGGGUUAGAGGUAGGGAGGGTUTU AAUAUAGGTRGGAUAUUAAGUTAGUATGGTGGAGAUUAAAAUUUAGGUAGUUTGG 323 UAATGGUUTUTTTUTTUAGUUTRGGTGGGRGTGGUTGGGGGAAUUUUAGGGRGGGR GGGGGGUAGGGGGTGGTGUTGAGTUAUUUAGUUTGGUUAGGTUUUTGUUTGUUAG UUUUUTGUUUUUAURGUTAUAGUURGUUURGGATUTAXGAGGUUUAGUUAGUUAU UTUTGGAUTUUTGAGAUXGAATTGUAAAUTGUURGGGUUTGGUUTTGAAUTUUTGU TGTTTAGGGAUUAAGTUUTGTGGUTUUUAGGGGGGUAUAGTGATUTUTUAAGUTGA GUTGGUUTUAGGGUUTUTGUAU

324 TGUAGAGGUTTTGAGGUUAGUTUAGUTTGAGAGATUAUTGTGUUUUUUTGGGAGU UAUAGGAUTTGGTUUUTAAAUAGUAGGAGTTUAAGGUUAGGUURGGGUAGTTTGU AATTXGGTUTUAGGAGTUUAGAGGTGGUTGGUTGGGUUTXGTAGATURGGGGRGGG UTGTAGRGGTGGGGGUAGGGGGUTGGUAGGUAGGGAUUTGGUUAGGUTGGGTGAU TUAGUAUUAUUUUUTGUUUUURGUURGUUUTGGGGTTUUUUUAGUUAGGGTGGTTA GAGGUTGAAGAAAGAGGUUATTGT 325 AUUUTGTGUAGGGUUTGUATUURGGAAGGUUTUUAUUAGUURGAAUUTGGUURGT URGUUUTAGATGGGGUAATRGGRGTTTUTUURGGGAUAGUUTUUTUUUTGGUUTUU TGGUUUTRGTUTGUATTGAGAGGUTTGGUUTUTGGTUXGUATGUTGUUUTTUURGT GUTGTGGUUTTGUAGUURGGUUTUTUUUUTGUTGTUUUUUTTGGUTUTGGUUTGGU UUUTGGGUUUUTGAGTUAUUUUTGAGGTGAUTUAGUAGTUUTTGGAAARGUATGUR GAGGARGUAUUUTGUUTGGUU 326 GUUAGGUAGGGTGRGTUUTRGGUATGRGTTTUUAAGGAUTGUTGAGTUAUUTUAGG GGTGAUTUAGGGGUUUAGGGGUUAGGUUAGAGUUAAGGGGGAUAGUAGGGGAGA GGURGGGUTGUAAGGUUAUAGUARGGGAAGGGUAGUATGXGGAUUAGAGGUUAA GUUTUTUAATGUAGARGAGGGUUAGGAGGUUAGGGAGGAGGUTGTUURGGGAGAA ARGURGATTGUUUUATUTAGGGRGGARGGGUUAGGTTRGGGUTGGTGGAGGUUTTU RGGGATGUAGGUUUTGUAUAGGGTT 327 GGAAUUATTGTTUTGUTGUUUAUAGUTGRGTGGAGGGATTURGGTUUTRGGGTTUA GTTGGTGAUAGTGTRGGGTAGGUUTGGGUAGGTGGGAGAGGTRGTGAAGUUUTTTG UAGGGUAUTTGGURGUTUATUTGGUAUAGGGGAAGAGGXGUAGUURGTGGUURGG UAGTUUAGGAUUTGUTGTTUUUTTUUTAUURGGGGRGGGGUUTGTGGGAAGATATG GAAGTRGGGTGAATGAGURGTGUUUAGTGATTTTAAAAAGUAGATTAAAATAAUAT AGAAAATGTUAGAGUTUATTG 328 UAATGAGUTUTGAUATTTTUTATGTTATTTTAATUTGUTTTTTAAAATUAUTGGGUAR GGUTUATTUAUURGAUTTUUATATUTTUUUAUAGGUUURGUUURGGGTAGGAAGGG AAUAGUAGGTUUTGGAUTGURGGGUUARGGGUTGXGUUTUTTUUUUTGTGUUAGAT GAGRGGUUAAGTGUUUTGUAAAGGGUTTUARGAUUTUTUUUAUUTGUUUAGGUUT AUURGAUAUTGTUAUUAAUTGAAUURGAGGAURGGAATUUUTUUARGUAGUTGTG GGUAGUAGAAUAATGGTTUU 329 GUATUUTUAUUTGRGTURGAAGRGUAGATGGAGUUUAAGGGAAAGGUUUTGTAGA GGAUUURGTGTGAUTTGGGGUAAAGRGTGGUUTUUUAGGGGTGRGTGGGUAGRGG GARGUUUATGGTGTGAURGGGTTTGTGUUTUUATAGGGAUXGTUTGUUUTGTGUAG AGAGUUUUTGTGGGGXGGGAAGTGGXGAGUAGURGGUAAGGAGGUUUAGUUAGA UAGAAGUAGGGGGGTUAGGGAUATGGGAGGTGGGGGAUUAGUUAGTGAGTUAGAR GTGAGGAUTTUAGTGUUAAGGAUTG 330 UAGTUUTTGGUAUTGAAGTUUTUARGTUTGAUTUAUTGGGUUTUTTUUUTGGTTUU ATGTUUUTGAUUUUUUTGUTTUTGTUTGGUTGGGUTTTUUTTGURGGUTGUTXGUUA UTTUUXGUUUUAUAGGGGUTUTUTGUAUAGGGUAGAXGGTUUUTATGGAGGUAUA AAUURGGTUAUAUUATGGGRGTUURGUTGUUUARGUAUUUUTGGGAGGUUARGUT TTGUUUUAAGTUAUARGGGGTUUTUTAUAGGGUUTTTUUUTTGGGUTUUATUTGRG UTTRGGARGUAGGTGAGGATGU 331 AGGTTUUUUATUUTAGUTUUURGGATUTUUATAGGGAGTGTUUAGGGAUUUTUAAT UTUUAGGGUUAUTTUTGUAGGAGUTRGGGTTRGAGGTTUUARGTGGUUAGAAGAGU TUAGGTUTUTGAGGGUTGGTGTGUURGGGTAUUUATUXGUATUAUTGUTUTUUTUU TGTURGGUTARGUUUAGGGUTGAGTGARGGTGGTGGUAAGTGUTTGTUUTUAGGGU AGRGAGGTUTTUTGTTUTGAUAGUAGUAGGGAUTUUTTUATGGUUAUUAGTAAUUU UAGTGGGRGGAGGRGUTUUT 332 AGGAGRGUUTURGUUUAUTGGGGTTAUTGGTGGUUATGAAGGAGTUUUTGUTGUTG TUAGAAUAGAAGAUUTRGUTGUUUTGAGGAUAAGUAUTTGUUAUUAURGTUAUTU AGUUUTGGGRGTAGURGGAUAGGAGGAGAGUAGTGATGXGGATGGGTAUURGGGU AUAUUAGUUUTUAGAGAUUTGAGUTUTTUTGGUUARGTGGAAUUTRGAAUURGAG UTUUTGUAGAAGTGGUUUTGGAGATTGAGGGTUUUTGGAUAUTUUUTATGGAGATU RGGGGAGUTAGGATGGGGAAUUT 333 TUUTTUUTTUTTTUUTTUTTTUTTUUTTUUUTTUTUUTTTUTTTUTTUUTTTUU UATTTTGAGARGTAUTUTGGUTUTGTRGUUUAGGUTGGAGRGUAATGGRGUUATUT RGGRGUAUTGUAAUUTUUAUUTUURGGGTTUAAGXGATTUTAUTGUUTUAGUUTUU RGAGTAGUTGGGAUTAUAGGRGRGUAUTAUUAAGUURGGUTAATTTTTTTTTGTATT TTTAGTAGAGAUTGGGTTTUARGATGTTGGURGGGUTGGTUTGGAAGTUTTGAUUTU AAGRGTGRGUUUTU 334 GAGGGRGUARGUTTGAGGTUAAGAUTTUUAGAUUAGUURGGUUAAUATRGTGAAA UUUAGTUTUTAUTAAAAATAUAAAAAAAAATTAGURGGGUTTGGTAGTGRGRGUUT GTAGTUUUAGUTAUTRGGGAGGUTGAGGUAGTAGAATXGUTTGAAUURGGGAGGTG GAGGTTGUAGTGRGURGAGATGGRGUUATTGRGUTUUAGUUTGGGRGAUAGAGUU AGAGTARGTUTUAAAATGAAAGAAGAGAAAAGAAAAGAAAAGAAAGAAAAGAGAG AGAAAGAAGGAAAGAAGGAAGGA 335 AGGUUTUTGUTGAUUTGTAGAAUTTGTTGAUURGGATTTTGATGTUAGTUTUATTGG GUUTGURGTTGUTUTTUTTGGGAUAGAAGATUTUTTTGATURGGUUAATTRGGTAGG GUTUAGGGGUATUUAGGTTGUTGUUTTTGATGTAGTXGGAGTATTTURGGTAGTGUT UTGGGTAUAGGTUUTUATUUARGGGUTUUTTURGTGGGRGTTTUARGGGAUTGGAU AGUTTGATGUTGUAGAGAAGUAUUUAUTTGAUATUAATGAAUUTTUUAUUTTGUAG TGGTUAGTUAGGUATGA 336 TUATGUUTGAUTGAUUAUTGUAAGGTGGAAGGTTUATTGATGTUAAGTGGGTGUTT UTUTGUAGUATUAAGUTGTUUAGTUURGTGAAARGUUUARGGAAGGAGUURGTGG ATGAGGAUUTGTAUUUAGAGUAUTAURGGAAATAUTUXGAUTAUATUAAAGGUAG UAAUUTGGATGUUUUTGAGUUUTAURGAATTGGURGGATUAAAGAGATUTTUTGTU UUAAGAAGAGUAARGGUAGGUUUAATGAGAUTGAUATUAAAATURGGGTUAAUAA GTTUTAUAGGTUAGUAGAGGUUT 337 GGGGRGGGGTTRGGURGGGGGRGGRGGUAGGAUUTGAGUAGUUAGGAGGGUTGGGGGAUA GTUAGGTUAGGURGGTGGUTAUURGGURGUTGGAGAGGGURGGATGGUARGTGGUAUUAAG UAAAAGGAGGUTGAGUUAGAAAGUAGGGAXGGGGUTAGARGAGUAAAGUTGGGUAGGAGG GRGAGTTGGGAGGGGURGAGURGGUTGTGRGTGGTUUUTTGGGAGGAGGGGGTGTGGUUAA GUAAGUUAAAUAGTTRGGAGGTUAGTGUAAGGAUAAGAUAGUUTGGGUAAARGAGUAG 338 UTGUTRGTTTGUUUAGGUTGTUTTGTUUTTGUAUTGAUUTURGAAUTGTTTGGUTTGUTTGGU UAUAUUUUUTUUTUUUAAGGGAUUARGUAUAGURGGUTRGGUUUUTUUUAAUTRGUUUTUU TGUUUAGUTTTGUTRGTUTAGUUUXGTUUUTGUTTTUTGGUTUAGUUTUUTTTTGUTTGGTGU UARGTGUUATURGGUUUTUTUUAGRGGURGGGTAGUUAURGGUUTGAUUTGAUTGTUUUUU AGUUUTUUTGGUTGUTUAGGTUUTGURGURGUUUURGGURGAAUUURGUUUU 339 RGAGTTGGGAGGGGURGAGURGGUTGTGRGTGGTUUUTTGGGAGGAGGGGGTGTGG UUAAGUAAGUUAAAUAGTTRGGAGGTUAGTGUAAGGAUAAGAUAGUUTGGGUAAA RGAGUAGGGGRGGAGRGTGAGAGUAGAUTGUAURGGATXGUTUAGGUUAGUUUAA GUTGAAGAGGAAGGGGUAAGUTUUAGAAGUAGGGGRGGGGURGAUUAAUUTRGUA GATUTGUTGGGRGAAGAGUAGUAGUTGGGUUAGUURGATGUTGTGURGGGGUAGG TAGTUTRGGAGGUTGUUUAGGGGU 340 UUUUTGGGUAGUUTURGAGAUTAUUTGUUURGGUAUAGUATRGGGUTGGUUUAGU TGUTGUTUTTRGUUUAGUAGATUTGRGAGGTTGGTRGGUUURGUUUUTGUTTUTGG AGUTTGUUUUTTUUTUTTUAGUTTGGGUTGGUUTGAGXGATURGGTGUAGTUTGUT UTUARGUTURGUUUUTGUTRGTTTGTAGGUTGTUTTGTUUTTGUAUTGAUUTURG AAUTGTTTGGUTTGUTTGGUUAUAUUUUUTUUTUUUAAGGGAUUARGUAUAGURGG UTRGGUUUUTUUUAAUTRGU 341 AAUAGGUUUAAGUUTGTGGUAGGTGGGGGTUAUUUAGUUUAGGRGUTTUUUAUUU URGGGUUTGGGUUAGAAGUUUAGGAGUTGGUTGRGGGURGGTTUTUUUUUAUUUA UTUTGGGGATGUUTUAGGUUTGGGTTTURGUUTTAGUUTXGUUAGGUUUUAATGAG UUTUTGTTTGGUUTGTAGTUAATTGAURGGTTGGAUTTGGGGUAGGTGUTRGAGGA GUUUUAUTGAGGGAGGGUAGGTUTUTTGTGRGTAUTGTUUAGUAUATAUAGGAAAT TTAGUATTTUTGUUUAUUUAGU 342 GUTGGGTGGGUAGAAATGUTAAATTTUUTGTATGTGUTGGAUAGTARGUAUAAGAG AUUTGUUUTUUUTUAGTGGGGUTUUTRGAGUAUUTGUUUUAAGTUUAAURGGTUA ATTGAUTAUAGGUUAAAUAGAGGUTUATTGGGGUUTGGXGAGGUTAAGGRGGAAA UUUAGGUUTGAGGUATUUUUAGAGTGGGTGGGGGAGAAURGGUURGUAGUUAGUT UUTGGGUTTUTGGUUUAGGUURGGGGGTGGGAAGRGUUTGGGUTGGGTGAUUUUU AUUTGUUAUAGGUTTGGGUUTGTT 343 UUTGAUUUAUUUAAUTUTUUUAGGGGARGTGGGGGUAUTGGAGUUUUAUAURGUA GGRGGTAGUTUAATGUAUURGRGTRGGAGTTUUTUUUURGRGAGRGTGGUAAGGUT UAGGGAAGTUURGGGUUUUTGGGGAGGGGGUUTTGURGXGUATUUTGTXGUAGGA AURGURGGGUUUTTUUTTURGRGGGAAGXGGUTTGGURGAUUUURGUUUURGUUR GGGUUTUTTGGGGGTTTURGGTGUURGGUUAURGTGGGGUTGGGGAUTGAAAGTGA TGGGAUTGAAGATGGGGUTGGAA 344 TTUUAGUUUUATUTTUAGTUUUATUAUTTTUAGTUUUUAGUUUUARGGTGGURGGG UAURGGAAAUUUUUAAGAGGUURGGGRGGGGGRGGGGGTRGGUUAAGUXGUTTUU RGRGGAAGGAAGGGUURGGRGGTTUUTGXGAUAGGATGXGRGGUAAGGUUUUUTU UUUAGGGGUURGGGAUTTUUUTGAGUUTTGUUARGUTRGRGGGGGAGGAAUTURG ARGRGGGTGUATTGAGUTAURGUUTGRGGTGTGGGGUTUUAGTGUUUUUARGTUUU UTGGGAGAGTTGGGTGGGTUAGG 345 TATUUAAATGTGTTTTATATAAAATGAATRGTTTTUAGTGUAUTGAGGAAGTTTTUT ATTTAAAGAAATUUTGUTGTGAAUTUTTTTGTGAAGAATGUTTTUUTAATGGAATTA GTUAUUAUTGAGTUATTTUTGUAAAUTTUAGGTTTGXGGTTTTGUUTAAGUAAGATU TGGURGGAGAAGTGAGATAAATTATAGATGTRGUTAATAAATTAUAGATTAUTUAA AGGUAAAAGAGGAAAGAAAAAAAAAAATTGAUTRGTGTATATGAAURGAATTGAGT UAGGGGTUTUUAURGGU 346 GURGGTGGAGAUUUUTGAUTUAATTRGGTTUATATAUARGAGTUAATTTTTTTTTTT UTTTUUTUTTTTGUUTTTGAGTAATUTGTAATTTATTAGRGAUATUTATAATTTATUT UAUTTUTURGGUUAGATUTTGUTTAGGUAAAAUXGUAAAUUTGAAGTTTGUAGAAA TGAUTUAGTGGTGAUTAATTUUATTAGGAAAGUATTUTTUAUAAAAGAGTTUAUAG UAGGATTTUTTTAAATAGAAAAUTTUUTUAGTGUAUTGAAAARGATTUATTTTATAT AAAAUAUATTTGGATA 347 TGGGAGTTUUAGTTRGGGGGUAGAUUAGTGTTUAGAGTURGGGUTUTGUTAUTUAG RGUURGAGGUAGRGUUTUUUUATTUAARGGGGGURGTGGUAATTUUUTGAUATGAT TUATGAUUAUATAATAUATURGGAAAUTTUTUTUUAUXGUUTUURGTUTGGGURGT RGUUUURGGUUTGGGAGAUTUUAGGTUTUAGAGTUTUTGUUUUUARGGGRGATUA GTGUTGUUUAGTGGAAAAATAATGUUAGURGRGUAUUAAAATTAGGTGTAAAATTA AUATTTTTTGGAAGUUAUTTT 348 AAGTGGUTTUUAAAAAATGTTAATTTTAUAUUTAATTTTGGTGRGRGGUTGGUATTA TTTTTUUAUTGGGUAGUAUTGATRGUURGTGGGGGUAGAGAUTUTGAGAUUTGGAG TUTUUUAGGURGGGGGRGARGGUUUAGARGGGAGGXGGTGGAGAGAAGTTTURGG ATGTATTATGTGGTUATGAATUATGTUAGGGAATTGUUARGGUUUURGTTGAATGG GGAGGRGUTGUUTRGGGRGUTGAGTAGUAGAGUURGGAUTUTGAAUAUTGGTUTGU UUURGAAUTGGAAUTUUUAT 349 RGGRGTGUTTUTTGGUAAAUATUTUUTTGAGGATGURGUTGUAGUAUTTGAGUTGU TURGAGAUTTTGUTGUTUTTUTUTGGTGUTGGGTGUTGUTGAGAGTRGGGUARGTUU TTUTTTGGAGGTTTUAUAGGURGGUTGUTUTUURGUXGUTGGUUUAGUTTGGTGGT UTTGGGUTURGGGGGUAGRGAGGGTGGUTRGTGAATGGGGTUAATGGTGGTGGGGG TGGTGGTGTUTGUTTTUUTUTTUAUTUUUTTUTTTGTUTGUUAAGAAUARGGARGUU AAUAGGUAUAGTUAGAAG 350 UTTUTGAUTGTGUUTGTTGGRGTURGTGTTUTTGGUAGAUAAAGAAGGGAGTGAAG AGGAAAGUAGAUAUUAUUAUUUUUAUUAUUATTGAUUUUATTUARGAGUUAUUUT RGUTGUUUURGGAGUUUAAGAUUAUUAAGUTGGGUUAGXGGRGGGAGAGUAGUR GGUUTGTGAAAUUTUUAAAGAAGGARGTGUURGAUTUTUAGUAGUAUUUAGUAUU AGAGAAGAGUAGUAAGGTUTRGGAGUAGUTUAAGTGUTGUAGRGGUATUUTUAAG GAGATGTTTGUUAAGAAGUARGURG 351 TGGTUTGUTTUAAGTUUTAUUTGGUUUUTGGUAAGTUUUAUTTGGTGAUATUTTGT GUUTGGGTUUTTGAGGGUTGUUUUAGATURGRGATTGTUUTGGGGAURGGTAGTTU UTUUURGGATGUUAGUAAAGUTUUUTUUAGUUTUUAXGUUTGUAUAGTUTUUAGT ATGUUTTUAAUAGUUATTAGTUAUUUTUTGTGAGTUAGAUUUURGGTUUTGUUAGG UUAAUUTGUTTGGGGUUTUAGUAGRGGGGGUTGGRGAGGUUAGTTTTUTUUAGRGG TTUTAAGURGUTRGAGGGTGG 352 UAUUUTRGAGRGGUTTAGAAURGUTGGAGAAAAUTGGUUTRGUUAGUUUURGUTG UTGAGGUUUUAAGUAGGTTGGUUTGGUAGGAURGUGGGTUUAUTUAUAUAUUUT GAUTAATGGUTGTTGAAGGUATAUTGGAGAUTGTGUAGGXGTGGAGGUTGGAGGGA GUTTTGUTGGUATURGGGGAGGAAUTAURGGTUUUUAGGAUAATRGRGGATUTGGG GUAGUUUTUAAGGAUUUAGGUAUAAGATGTUAUUAAGTGGGAUTTGUUAGGGGUU AGGTAGGAUTTGAAGUAGAUUAG 353 AUUTGGTRGGUUAURGGUAGUTRGGGGAAGAAGGGRGRGTGGRGRGUUUAUTUUA RGGTGUTGAAGAGUAGURGRGURGUUAGUTRGUAUARGTTGTRGATGUUUAGUAUR GRGUURGURGRGURGUUUUUTGRGURGAAGRGTURGGUXGURGUAGGGTAGGGUT UAGRGRGUAGUAGUTGRGRGATUAGTTRGGAUAURGGUTGUUURGGGAAGAGGTU TURGURGUTRGUUAUTGURGUUAGRGURGAGUURGGGGGGUTGUURGAGGAGGRG GUUARGGUAUUAGGUAGRGAGTGU 354 GUAUTRGUTGUUTGGTGURGTGGURGUUTUUTRGGGUAGUUUUURGGGUTRGGRGU TGGRGGUAGTGGRGAGRGGRGGAGAUUTUTTUURGGGGUAGURGGTGTURGAAUTG ATRGRGUAGUTGUTGRGRGUTGAGUUUTAUUUTGRGGXGGURGGARGUTTRGGRGU AGGGGGRGGRGRGGRGGGRGRGGTGUTGGGUATRGAUAARGTGTGRGAGUTGGRGG RGRGGUTGUTUTTUAGUAURGTGGAGTGGGRGRGUUARGRGUUUTTUTTUUURGAG UTGURGGTGGURGAUUAGGT 355 TGGUAGAGATAUAAATTUUTGATGGUAGAGGAGGGAGAGAGAGTGTGGGTGARGA TGAUAATTGAAUTGAGAUUUAAAGGAGGTAGGGGAGAUATATGGGRGTUTUTGGG AAGATGGTUUURGGGAAAGUAUAGUUTTTAGAUAGGUUUXGAGGUAGGAGUUTGT UTGAUTUAURGGAGGAGUTTGGAGGAGGUTGAGGTGGUUTAAGTRGATTAAGUAGG GTGGGGAGGGAAGAGGRGATGGTGURGTGAGAUUAAGUAGGGUUTTGAGGTUTGG GGGGAGAAUTTTGGUTTTTAUTUT 356 GAGTAAAAGUUAAAGTTUTUUUUUUAGAUUTUAAGGUUUTGUTTGGTUTUARGGU AUUATRGUUTUTTUUUUUUUUAUUUTGUTTAATRGAUTTAGGUUAUUTUATGGTT TUUAAGUTUUTURGGTGAGTUAGAUAGGUTUUTGUUTXGGGGUUTGTUTAAAGGUT GTGUTTTUURGGGGAUUATUTTUUAGAGARGUUUATATGTUTUUUUTAUUTUUTT TGGGTUTUAGTTUAATTGTUATRGTUAUUUAUAUTUTUTUTUUUTUUTUTGUUATUA GGAATTTGTATUTUTGUUAG 357 AGAGGAGGGAGAGAGAGTGTGGGTGARGATGAUAATTGAAUTGAGAUUUAAAGGA GGTAGGGGAGAUATATGGGRGTUTUTGGGAAGATGGTUUURGGGAAAGUAUAGUU TTTAGAUAGGUUURGAGGUAGGAGUUTGTUTGAUTUAUXGGAGGAGUTTGGAGGA GGUTGAGGTGGUUTAAGTRGATTAAGUAGGGTGGGGAGGGAAGAGGRGATGGTGU RGTGAGAUUAAGUAGGGUUTTGAGGTUTGGGGGGAGAAUTTTGGUTTTTAUTUTGA GGAAGGTGGGAGUUAUAGAGGUTT 358 AGUUTUTGTGGUTUUUAUUTTUUTUAUAUTAAAAUUUAAAUTUUUTUUTTTAGGAUU TUAAGGUUUTGUTTGGTUTUARGGUAUUATRGUUTUTTUUUTUUUUAUUUTGUTTA ATRGAUTTAGGUUAUUTUAGUUTUUTUUAAGUTUUTUXGGTGAGTUAGAUAGGUTU UTGUUTRGGGGUUTGTUTAAAGGUTGTGUTTTUURGGGGAUUATUTTUUUAGAGAR GUUUATATGTUTUUUUUAUUTUUTTTGGGTUTUAGTTUAATTGTUATRGTUAUUUAU AUTUTUTUTUUUTUUTUTG 359 TGGGRGTUTUTGGGAAGATGGTUUURGGGAAAGUAUAGUUTTTAGAUAGGUUURG AGGUAGGAGUUTGTUTGAUTUAURGGAGGAGUTTGGAGGAGGUTGAGGTGGUUTA AGTRGATTAAGUAGGGTGGGGAGGGAAGAGGRGATGGTGUXGTGAGAUUAAGUAG GGUUTTGAGGTUTGGGGGGAGAAUTTTGGUTTTTAUTUTGAGGAAGGTGGGAGUUA UAGAGGUTTUTAGAUAGAAGAAGGAUAAGURGGAUTUAGGATAUUAGGGTGGGGG TATUTGTGGGGGATAAAGGGAGAA 360 TTUTTUUTTTATUUUUUAUAGATAUUUUUAUUUTGGTATUUTGAGTURGGUTTGTU

UTTUTUTGTUTAGAAGUUTUTGTGGUTUUUAUUTTUUTUAGAGTAAAAGUUAAAG TTUTUUUUUUAGAUUTUAAGGUUUTGUTTGGTTTUAXGGUAUUATGGUUTUUUUU TUUUUAUUUTGUTTAATRGAUTTAGGUUAUUTUAGUUTUUTUUAAGUTUUTURGGT GAGTUAGAUAGGUTUUTGUUTRGGGGUUTGTUTAAAGGUTGTGUTTTUURGGGGAU UATUTTUUUAGAGARGUUUA 361 GGUTTTGTGAAAUUAAUUAGGAAGAATGAAAUAUAGAGUTGGTURGAUAUUUAGU TRGAGGGAGGGGGGURGGAAGUTTUTGGAAGTTGGUTGUUUUTAAGUAGGGGUUA UTUTAGUUUAUAAGGUUAAGTTGGUAGAGGUAGAXGAGGGGAUTUTGXGGUTUAA GTUARGGGUUAGGAGUURGUAGUTGURGGGUTGGAAAGGTUAGAGURGGUTUTGR GTUTGGUTGRGURGGUAAGAAGUUAUAATTARGUAGGUAAAAGAGUURGGGGATT AGUUUUAGUAUUTGGGAUUUTGAAT 362 ATTUAGGGTUUUAGGTGUTGGGGUTAATUUURGGGUTUTTTTGUUTGRGTAATTGTG GUTTUTTGURGGRGUAGUUAGARGUAGAGURGGUTUTGAUUTTTUUAGUURGGUAG UTGRGGGUTUUTGGUURGTGAUTTGAGUXGUAGAGTUUUUTXGTUTGUUTUTGUUA AUTTGGUUTTGTGGGUTAGAGTGGUUUUTGUTTAGGGGUAGUUAAUTTUUAGAAGU TTURGGUUUUUUTUUUTRGAGUTGGGTGTRGGAUUAGUTUTGTGTTTUATTUTTUUT GGTTGGTTTUAUAAAGUU 363 AGGUTGAARGGAATTGGGAGUAGAGUUUTGRGGTAGGAUAGAGAUTTRGUAAAGU URGGAGUAUAUAGUAGUAUUURGTUTTUTAAAGGAUAATTTTGGGAAAAUTUTTGU UTAATATTUTGGUAUTAAGGATUATTUTGTUAUATUUUXGUTUTGGAUTAUAAGUU TGUAAGUUUUATURGGGGUAGGGTTTUUTUATTUUTGTGUAURGTGGAAGUUUTGTG UUTGUUUAGGGUUTGGUAUTTGTARGTAUTTGAAAAUUTRGTGTGGAGTAAAGAGA GGGGTGATGTGUAAAGGUUTT 364 AAGGUUTTTGUAUATUAUUUUTUTUTTTAUTUUAUARGAGGTTTTUAAGTARGTAU AAGTGUUAGGUUUTGGGUAGGUAUAGGGUTTUUARGGTGUAUAGGAATGAGGAGU UUTGUUURGGATGGGGUTTGUAGGUTTGTAGTUUAGAGXGGGGATGTGAUAGAATG ATUUTTAGTGUUAGAATATTAGGUAAGAGTTTTUUUAAAATTGTUUTTTAGAAGARG GGGTGUTGUTGTGTGUTURGGGUTTTGRGAAGTUTUTGTUUTAURGUAGGGUTUTGU TUUUAATTURGTTUAGUUT 365 AGUUAGGUTAAAUUAGRGTGTUUUAATGAGGGGUUUTGGGUTGAGTGGAGGAAAT GGGTGRGGTGGAGGTGGGTTTGGUTGGGUAUAGRGGGUARGTGTGGGTAAGRGGGT GGGGURGGTTGTGRGGGTGGUUTATUTGGGGUAAGUAGUXGAGGURGAUTGTGTUR GGRGTGTGGTTGAGUARGGGUAGGTGTUTGGRGGTGAUUUTGUARGTUTGGTGTTT AUUTGGUUUTGGGTUTGARGTGGGURGRGUUTGGUTGUTGGRGGGAUAGTGTGTTA TUTGUUTGRGGARGUTTURGG 366 URGGAAGRGTURGUAGGUAGATAAUAUAUTGTUURGUUAGUAGUUAUURGKUUUU UARGTUAGAUUUAGGGUUAGGTAAAUAUUAGARGTGUAGGGTUAURGUUAGAUAU UTGUURGTGUTUAAUUAUARGURGGAUAUAGTRGGUUTXGGUTGUTTGUUUUAGAT AGGUUAUURGUAUAAURGGUUUUAUURGUTTAUUUAUARGTGUURGUTGTGUUUA GUUAAAUUUAUUTUUAURGUAUUUATTTUUTUUAUTUAGUUUAGGGUUUUTUATT GGGAUARGUTGGTTTAGUUTGGUT 367 UUTTGGUTUAGGTTGGGGAGGGRGTUATGAGTUATGAGGTGGGRGTTGUATTTGTU AGTTGTGUAGURGRGUAUUAURGAGTAGTUTGGRGGUAGRGRGTURGRGTTRGATT GRGTUTGGUURGUAGGAGGUURGGTUUAGUAGUUUTTUXGUAUUAGGGTUAURGG RGRGRGATAUUUTGGGGGRGGGATRGGGGUTRGTGUTUTGUTTUURGAAAUUUTTU TUUUTUUAGTUTUAGRGTTUTTUUTUUTUUUTUTATIUTTTUAUTTTGGAGTTAUT TUUTUUUUTUUUTUUTTUUU 368 GGGAAGGAGGGAGGGGAGGAGGTGTAGGTGAAAGTGAAAGGATAGAGGGAGGAGG AAGAARGUTGAGAUTGGAGGGAGAAGGGTTTRGGGAAGUAGAGUARGAGUUURGA TUURGUUUUUAGGGTATRGRGRGURGGTGAUUUTGGTGXGGAAGGGUTGUTGGAUR GGGUUTUUTGRGGGUUAGARGUAATRGAARGRGGARGRGUTUURGUUAUAUTAUT RGGTGGTGRGRGGUTGUAUAAUTGAUAAATGUAARGUUUAUUTUATGAUTUATGAR GUUUTUUUUAAUUTGAGUUAAGG 369 UAGGUTGGAGTGUAATGGRGRGATUTRGGUTUAUTGUAAUTTUTGUUTUTRGGGTT UAAGUAATTUTTUTAUUTTAGUUTUUTGAGTAGUTGGGATTAUAGGTAUUTGURGU UATGUURGGUTAATTTTTTAATTTGTTTTTAGTAGAGAXGGGGTTTUAUUATGTTGG UUAGGURGGTUTAUAAUTUUTGATUTUAGGTGATUTAUURGUUTRGGUUTUUUAAA TTAUAGGTGTTATUATTAGGATTUTTGGUAGAUAGGAGTGTTGTAGGGGATGGAAGT GGATAGTAGGAGGUTUTG 370 UAGAGUUTUUTAUTATUUAUTTUUATUUUUTAUAAUAUTUUTGTUTGUUAAGAATU UTAATGATAAUAUUTGTAATTTGGGAGGURGAGGRGGGTAGATUAUUTGAGATUAG GAGTTGTAGAURGGUUTGGUUAAUATGGTGAAAUUUXGTUTUTAUTAAAAAUAAAT TAAAAAATTAGURGGGUATGGRGGUAGGTAUUTGTAATUUUAGUTAUTUAGGAGGU TAAGGTAGAAGAATTGUTTGAAUURGAGAGGUAGAAGTTGUAGTGAGURGAGATRG RGUUATTGUAUTUUAGUUTG 371 TGAATGAUUTGGGUAGUATTTUTUUAUUTGRGUTTGUATTTGUTAGAUAGTUTGTGA UTUTUTGTGGGAGAAAAUAUAAGAAAURGGUUUUTUTGUTGGTTUUUUAUUTGGU UTGGUTUTUUTGTTUTUUAUUUTGUAUAUTUATGUUTXGGAAUUTGUTTUTUUTUT GAGUTUUUTUAUAGTGGUURGGUUUARGTGGUUTTTAATUTGUUUAUATUAGAGU UTUUAUUTURGGUUTATGGUUUATUAGAGGUAGUTGGAGURGGGUATUUTUUUUA RGTGGGUUTTTGAGGATGGGA 372 TUUUATUUTUAAAGGUUUARGTGGGGAGGATGUURGGUTUUAGUTGUUTUTGATGG GUUATAGGURGGAGGTGGAGGUTUTGATGTGGGUAGATTAAAGGUUARGTGGGUR GGGUUAUTGTGAGGGAGGUTUAGAGGAGAAGUAGGTTUXGAGGUATGAGTGTGUA GGGTGGAGAAUAGGAGAGUUAGGUUAGGTGGGGAAUUAGUAGAGGGGURGGTTTU TTGTGTTTTUTUUUAUAGAGAGTUAUAGAUTGTUTAGUAAATGUAAGRGUAGGTGG AGAAATGUTGUUUAGGTUATTUA 373 GGGRGGGGUUTGTGRGGTUTGRGGRGRGGAGURGAGTGGGUTGRGGGGATGRGGGG GAUUAGUTGRGTGGGRGGRGGRGURGAGAGUUURGGAGGRGRGGGGUTGAGRGAG GGUURGRGGGGGRGUTGGUTGRGUTTGGUTURGGTATGXGUUTAUTTUUTUTGRGT UTXGUTAGUTGURGTGUTGUTRGURGTGTAUTARGGTUTUATUTGGGTAUUUARGR GGTUTUURGRGGUAUURGURGGUUUAUAGUUUAGRGRGURGTUUUUTURGTGTGUT GTTURGUTTRGGGRGTGURGUUT 374 AGGRGGUARGUURGGGRGGGUAGUAUARGGAGGGGARUUKUKGUTUUUUTUTUUU URGGRGGGTGURGRGGGAGAURGRGTGGGTAUUUAGATGAGAURGTAGTAUARGG RGAGUAGUARGGUAGUTAGXGAGARGUAGAGGAAGTAGGXGUATAURGGAGUUAA GRGUAGUUAGRGUUUURGRGGGUUUTRGUTUAGUUURGRGUUTURGGGGUTUTRG GRGURGURGUUUARGUAGUTGGTUUUURGUATUUURGUAGUUUAUTRGGUTURGR GURGUAGAURGUAUAGGUUURGUUU 375 AAGTGTATTTTUAAGGTATGAGGGGUUUAGAGGAUAUTGTUUUAAAAGUAGTGGTT GTGAGAGTGGUTTTGGAGTUAGGUTGAUAGTUTGGAAAUTTUUAGGTURGUTUTGA AGTGURGGUTGUATGAUUAGUUUTUUAGUUTGTGTUXGUTTRGGUUTTUTTTGTGU AAGTGAGAGUATTGUTGATUUUUURGGGGTGGRGAGGGGGRGUARGTUAGTGAUUT RGUATGGTGUUTGUUAGGUARGTGGTURGTGTTTUATGATTUTTTGAGAGUTTTGGA GUAGUTUUAAGAAGAUTUT 376 GAGTUTTUTTGGAGUTGUTUUAAAGUTUTUAAAGAATUATGAAAUARGGAUUARGT GUUTGGUAGGUAUUATGRGAGGTUAUTGARGTGRGUUUUUTRGUUAUUURGGGGG GATUAGUAATGUTUTUAUTTGUAUAAAGAAGGURGAAGXGGAUAUAGGUTGGAGG GUTGGTUATGUAGURGGUAUTTUAGAGRGGAUUTGGAAGTTTUUAGAUTGTUAGUU TGAUTUUAAAGUUAUTUTUAUAAUUAUTGUTTTTGGGAUAGTGTUUTUTGGGUUUU TUATAUUTTGAAAATAUAUTTT 377 TAATTTTAAAUAAAAUTTTUUATGAGUAAUTAAATATTTAAAATGTGTTTTTUUATA AAAGTGAATUAGUTUAGTTUTGUAGGUTGAAAATAUAAUAAGGAGGATURGGGTTG UAGAAAGUAGAGGGUUAUUTAGAURGTGTUTGAGAGAXGGGGAGAAAGUAGUTGT UTGUTGTGUAUUAGAGGUUTUTAGGGAUUURGGUAGUAAUUURGTGGRGGGUUAU AUTTGGGAGUTGATTTGTTTTUAGAAUUAUUAGUTAAGUUAUATGAGUUAGGAGUU TGGTTATUUATTUAAAGUUUA 378 TGGGUTTTGAATGGATAAUUAGGUTUUTGGUTUATGTGGUTTAGUTGGTGGTTUTGA AAAUAAATUAGUTUUUAAGTGTGGUURGUUARGGGGTTGUTGURGGGGTUUUTAG AGGUUTUTGGTGUAUAGUAGAUAGUTGUTTTUTUUUXGTUTUTUAGAUARGGTUTA GGTGGUUUTUTGUTTTUTGUAAUURGGATUUTUUTTGTTGTATTTTUAGUUTGUAGA AUTGAGUTGATTUAUTTTTATGGAAAAAUAUATTTTAAATATTrAGTTGUTUATGGA GAGTTTTGTTTAAAATTA 379 GUUTUUAGAUURGAAATUUUUUAUTGAAGUUATTUUUAGGAGGAGGGGUUTUAUT GGGGUUTUAAGGUAGUATUAGUATTTURGGTGAUAGGUAUAGUAATTTATUAGUTU AUTGGUTUTUTAUTGAGAAUAAGGUAAGURGGGGUUTGUXGAGGGTATGAUAGGU AGGGAGTGATGGGUURGGUUUAGGGUAGGAGGGAGAUAGAAATGGGUAGGAAGA GGAGGUTGTUUUUAGUAGUAUTTUTGAGAGGAGGAGUAUUTTTRGGGGAUAUTUT GGARGGUAUUUUUAAGUAUAGUUUU 380 GGGGUTGTGUTTGGGGGTGURGTUUAGAGTGTUUURGAAAGGTGUTUUTUUTUTUA GAAGTGUTGUTGGGGAUAGUUTUUTUTTUUTGUUUATTTUTGTUTUUUTUUTGUUU TGGGURGGGUUUATUAUTUUUTGUUTGTUATAUUUTXGGUAGGUUURGGUTTGUUT TGTTUTUAGTAGAGAGUUAGTGAGUTGATAAATTGUTGTGUUTGTUAURGGAAATG UTGATGUTGUUTTGAGGUUUUAGTGAGGUUUUTUUTUUTGGGAATGGUTTUAGTGG GGGATTTRGGGTUTGGAGGU 381 TGAGAGUAGUUAGAUARGTAGTGATUAGGGAAAGTRGAAAGTGUAGATGGGTTRG UAAARGTGGAUTUTUTAGTTTTGGGTUTGUAGATGGGGURGGUUAUUAXGTGUTUT UTGAGTTUTUTTTUUAAGTAUAGATUUUTURGGAGARGGAAUATTGTTURGUUTTTA ATTUTTUUUAGGAGUTGRGGAGGAAGGXGTGAGAAURGGAGUURGGGGTGAUTTGR GGGGGAGGGGATRGUTTUUURGTRGUUUAUAUUTGUUTAAUUUARGUUUARGGRG GURGUAAAGGRGAUAURGRGT 382 ARGRGGTGTRGUUTTTGRGGURGURGTGGGRGTGGGTTAGGUAGGTGTGGGRGARG GGGAAGRGATUUUUTUUUURGUAAGTUAUUURGGGUTURGGTTUTUAXGUUTTUUT URGUAGUTUUTGGGAAGAATTAAAGGRGGAAUAATGTTURGTUTURGGAGGGATUT GTAUTTGGAAAGAGAAUTUAGAGAGUAXGTGGTGGURGGUUUUATUTGUAGAUUU AAAAUTAGAGAGTUUARGTTTGRGAAUUUATUTGUAUTTTRGAUTTTUUUTGATUA UTARGTGTUTGGUTGUTUTUA 383 AUAAGRGGTTGGATTTRGAGAGGAUATUAAGAGUARGTUAAGAGUARGTUAAGAG UAUARGGAUAGGUAUTGGUARGURGGUAGGTUATTGAURGGUAGAAUAGAGTTTG GUUAGGGUTGTUAGAGAAGAGTRGGGURGUUAAGUAGUUXGAUTTUUAGRGGAAA AUUATUTGUUTTUTGGUTUUTUUATUTGUTGAGAGUTAUTTUUAUTUAATAAAAUU TTGUAUTUATTUTUUAAAUUUAUATGAGATUUAATTUTTURGGTAUAUUAAGGUAG GAAUUURGAGATAUAGAAAGUUU 384 GGGUTTUTGTATUTRGGGGTTUUTGUUTTGGTGTAURGGAAGAATTGGATUTUATG TGGGTITGGAGAATGAGTGUAAGGTTTTATTGAGTGGAAGTAGUTUTUAGUAGATG GAGGAGUUAGAAGGUAGATGGTTTTURGUTGGAAGTXGGGUTGUTTGGRGGUURGA UTUTTUTUTGAUAGUUUTGGUUAAAUTUTGTTUTGURGGTUAATGAUUTGURGGRG TGUUAGTGUUTGTURGTGTGUTUTTGARGTGUTUTTGARGTGUTUTTGATGTUUTUT RGAAATUUAAURGUTTGT 385 AUTTGAAGTUAGGAGTTRGTGAAUAGUUTGGUUAAUATGGTGAAAUUUTGTUTUTA UTAAAAAAAGAAAAATTAGURGGGTGTGGTGGGRGUUTGTAAUUUUAGUAUTTTGG GAGGUTGAGGTGGGTGGATUAUTTGAAGTUAGGAGTTXGTGAAUAGUUTGATUAAU ATGGTGAAAUUUTGTUTUTAUTAAAAAUAUAAAAATTAGURGGGTGTGGTGGTGGG TGUUTGTAATUUUAGUTAUTUAGGAGAUTGAGGUAGGAGGATUAUTTGAAURGGG GAGGUAGAGGTTGUAGAGAGT 386 UTUTUTGUAAUUTUTGUUTUUURGGTTUAAGTGATUUTUUTGUUTUAGTUTUUTGA GTAGUTGGGATTAUAGGUAUUUAUUAUUAUAUURGGUTAATTTTTGTGTTTTTAGTA GAGAUAGGGTTTUAUUATGTTGATUAGGUTGTTUAXGAAUTUUTGAUTTUAAGTGA TUUAUUUAUUTUAGUUTUUUAAAGTGUTGGGGTTAUAGGRGUUUAUUAUAUURGG UTAATTTTTUTTTTTTTAGTAGAGAUAGGGTTTUAUUATGTTGGUUGUTTAAA GAAUTUUTGAUTTUAAGTG 387 AAATUTTTTTUUTGUUTGUATTTTUTTAUATAAAGUAATUTAUTAUTGUUATRGGTT UATTUAUTUAURGGAAUUTGTUTTGUUAGGAUUTGAUUTUAGUAGAUTGAGTUATA UUAGUATUATUUTTGTTGGGGUUUAGGTUTGUATUUXGUTTURGGUUUUAGUUUUA UTGTTAGUTUUATUAGGTUUTUTGGGGUAUAUUAAGGAGGURGTTTTUTLTUUUTTT TTUTGAATTAGATUUUUAGAAAUAAGAUATUAGGUTTUUTGGGGAAATUTAATTTT GUTUATGAATTTGAUUAT 388 ATGGTUAAATTUATGAGUAAAATTAGATTTUUUUAGGAAGUUTGATGTUTTGTTTUT GGGGATUTAATTUAGAAAAAGGGAGAGAAAARGGUUTUUTTGGTGTGUUUUAGAG GAUUTGATGGAGUTAAUAGTGGGGUTGGGGURGGAAGXGGGATGUAGAUUTGGGU UUUAAUAAGGATGATGUTGGTATGAUTUAGTUTGUTGAGGTUAGGTUUTGGUAAGA UAGGTTURGGTGAGTGAATGAAURGATGGUAGTAGTAGATTGUTTTATGTAAGAAA ATGUAGGUAGGAAAAAGATTT 389 UAAGGTUUAGGTUUUAGUUTUUUUAURGURGUURGRGUUUTUUTAGGUUTRGGAG RGGRGUTTTTUTGRGGUUTRGAAGGTGGGGTGGGAAAGTTTGGGGAGTUURGGUTU TUAUAGUUTGTRGTGAGAAUTGUUUURGGGGAATTRGTUXGURGTARGGAAAAAUT GGURGGAGUAGAGTRGTURGRGGTTURGRGGTRGRGGGTGGAAGGTGAAGGTRGAG GGAGGTUAGGUTGUTTUTGRGTGTUUTGARGGUTGGRGTGTTUTUTTGAGATGGGUT RGGGUTAUTTGGUUAGUTTU 390 GAAGUTGGUUAAGTAGUURGAGUUUATUTUAAGAGAAUARGUUAGURGTUAGGAU ARGUAGAAGUAGUUTGAUUTUUUTRGAUUTTUAUUTTUUAUURGRGAURGRGGAA URGRGGARGALTUTGUTURGGUUAGTTTTTURGTARGGXGGARGAATTUUURGGGG GUAGTTUTUARGAUAGGUTGTGAGAGURGGGAUTUUUUAAAUTTTUUUAUUUUAU UTTRGAGGURGUAGAAAGGRGURGUTURGAGGUUTAGGAGGGRGRGGGRGGRGGT GGGGAGGUTGGGAUUTGGAUUTTG 391 URGAGGGAGUUAGGUUAUAGUTGAUAGGAAGGUAGAAGGTGGUAGGAGGGGAGG TTGRGUTGUAUUTUTGGGTTGUUUAGGUUAAUUTGUUAGGUAGGAGGGGGAAGUU RGTGUUUAUTTTAUUATGAURGGGAAGATGATGGUAGUUAUXGTGGATTTGAGGAT UUAGAGUAURGUUAGGUAGAGGATUTGUAUUAGGGTGAAGAGGTGGATURGGRGU AGRGGUARGTGURGUAGGAAGGUATGGTURGGUTGGTGUTTGGUTGGUATUAGGAA GAGUTTGUAGRGTTUUUAGAAUTA 392 TAGTTUTGGGAARGUTGUAAGUTUTTUUTGATGUUAGUUAAGUAUUAGURGGAUUA TGUUTTUUTGRGGUARGTGURGUTGRGURGGATUUAUUTUTTUAUUUTGGTGUAGA TUTTTUTGUUTGGRGGTGUTUTGGATUUTUAAATUUAXGGTGGUTGUUATUATUTTU URGGTUATGGTAAAGTGGGUARGGGUTTUUUUUTUUTGUUTGGUAGGTTGGUUTGG GUAAUUUAGAGGTGUAGRGUAAUUTUUUUTUUTGUUAUUTTUTGUUTTUUTGTUAG UTGTGGUUTGGUTUUUTRGG 393 AAATTAUURGGGRGTGGTGGTGGGTGUUTGTAATUUUAGUTAUTUAGGAGGURGAG GUAGGAGAAURGUTTGAAUURGGGAGGUAGAGUATAGGTTGTTGGAGGGTTGAAG GTGUAUUUAGUAGAGAUTGGUATAUAGGAGGTUUTGUAAXGGUUUUAGGAAAUUT UTGGGTUUAGTAAGAGUTTUAGUAGGAGGTAGAAUUATAURGGGUAGGAGTGUUT GGAAAGGUTTUAAGGUAAUTUUUTUUAAAGTLTTrGGUUUAAUUUTAUAUTGTUAG GUTGTTAAAGGUUATTTAAAAGUT 394 AGUTTTTAAATGGUUTTTAAUAGUUTGAUAGTGTAGGGTTGGGUUAGGAUTTTGGA GGGAGTTGUUTTGAAGUUTTTUUAGGUAUTUUTGUURGGTATGGTTUTAUUTUUTG UTGAAGUTUTTAUTGGAUUUAGAGGTTTUUTGGGGUXGTTGUAGGAUUTUUTGTAT GUUAGTUTUTGUTGGGTGUAUUTTUAAUUUTUUAAUAAUUTATGUTUTGUUTUURG GGTTUAAGRGGTTUTUUTGUUTRGGUUTUUTGAGTAGUTGGGATTAUAGGUAUUUA UUAUUARGUURGGGTAATTT 395 AGGAAAAAAUAGUAGUUUAAGAATRGGGUUTUUUTGTTAUAGUAGGAGTRGUATU TATTTATATATGTTATGTUTTATTGUTUAGUAAUUAGUTUTRGGURGGGGRGTGGGU RGGGAAGAGGGGTUTUUTGGTGUAGXGGGTTGGRGTGAUTUATUAURGURGXGUAU TUTGGUUTUTGGGUUTAGGTTAAUAGAUTUURGGGTTTUAGGUTGGGUUUAGGRGG UUAGGUUUTUUUTGUTGAGGAATUTGGGTTGGGGUAGTGUUAGUTUUUTGUTTUTU AUUTGGUUAUAGAAGGGGTA

396 TAUUUUTTUTGTGGUUAGGTGAGAAGUAGGGAGUTGGUAUTGUUUUAAUUUAGAT TUUTUAGUAGGGAGGGUUTGGURGUUTGGGUUUAGUUTGAAAUURGGGAGTUTGT TAAUUTAGGUUUAGAGGUUAGAGTGXGRGGRGGTGATGAGTUARGUUAAUUXGUT GUAUUAGGAGAUUUUTUTTUURGGUUUARGUUURGGURGAGAGUTGGTTGUTGAG UAATAAGAUATAAUATATATAAATAGATGRGAUTUUTGUTGTAAUAGGGAGGUURG ATTUTTGGGUTGUTGTTTTTTUUT 397 AUUUAGGAATTUTTTTUUTTTTTTTTGAGARGGRGTUTUTGTRGUUUAGGUTGGAG TGUAGTGGRGUAGTUTRGUUTAAUTGUAAGUTURGUUUURGGGTTUATGUUATTUT UUTGUUTUAGUUTUTTGAGTAGUTGGAAUTAUAGGXGUUTGUUAUUAUAUURGGU UAATTTTTTGTATTTTTAGTAGAGARGGGGTTTUAURGTGTTAGUTAGGATGGTUTR GATUTUUTGAUUTRGTGATUUAUUUAUUTUAGUUTUTUAAAGTGUTGGGATTAUAG GUTTGAAUUAUTGRGUUU 398 GGGRGUAGTGGTTUAAGUUTGTAATUUUAGUAUTTTGAGAGGUTGAGGTGGGTGGA TUARGAGGTUAGGAGATRGAGAUUATUUTGGUTAAUARGGTGAAAUUURGTUTUTA UTAAAAATAUAAAAAATTGGURGGGTGTGGTGGUAGGXGUUTGTAGTTUUAGUTAU TUAAGAGGUTGAGGUAGGAGAATGGUATGAAUURGGGGGRGGAGUTTGUAGTTAG GRGAGAUTGRGUUAUTGUAUTUUAGUUTGGGRGAUAGAGARGURGTUTUAAAAAA AAAAAAAAAAGAATUUTGGGT 399 AAATAUAGUAGGAGAGAATTUUTUTGAGAUUTAAGATAURGTGUUUTTUUUUUTTG GUUTUTUAGUTGUTGURGAGTUUTGGAGAAAATRGGGUATUTGAAUAGAGGURGTG TTTGTUUUTGUTURGGUUTTGTGTTUTUATTUUTGUUAXGUUATUATGGATAATGAA AGTTGAUTGGUTGURGGGGTTTUUTTTUTUTUTGUUUUTGTUATTTUUATTTGUUAG GTUTUATGUUTTTTTTGUAUAGAGTTGTTGTGUTTGGGUTUTAATTTGUUAGGUAGT GATAAATTUUAAGAAAA 400 TTTTUTTGGAATTTATUAUTGUUTGGUAAATTAGAGUUUAAGUAUAAUAAUTUTGT GUAAAAAAGGUATGAGAUUTGGUAAATGGAAATGAUAGGGGUAGAGAGAAAGGA AAUUURGGUAGUUAGTUAAUTTTUATTATUUATGATGGXGTGGUAGGAATGAGAAU AUAAGGURGGAGUAGGGAUAAAUARGGUUTUTGTTUAGATGUURGATTTTUTUUAG GAUTRGGUAGUAGUTGAGAGGUUAAGGGGGAAGGGUARGGTATUTTAGGTUTUAG AGGAATTUTUTUUTGUTGTATTT 401 GUUUTGAGAUAUTAAATGGRGGGGGGGTGGGGGGAGGAAAGGGAAGGRGGUAGAG UTUUURGAGURGGGAUAGTUAUTTAUTUTAUAGGUAGTGGGGUURGAUAUAGAUA GRGURGUUUURGUUAGUUAGUUTRGUARGUUUTRGGAAGXGUAGGUTUURGGRGU TGRGUTGGAGGGTTUUURGGUAUUUUAGUUTUURGTUUUUAGUURGUTGUAUUTU RGGGUUUUUUTTAUUUTTGAGAGGUAURGGGAGTTGTRGRGGGGGGGUUTRGGGA AATTUUURGGAUUUUTGTGUUAGGA 402 TUUTGGUAUAGGGGTURGGGGAATTTUURGAGGUUUUUURGRGAUAAUTUURGGT GUUTUTUAAGGGTAAGGGGGGUURGGAGGTGUAGRGGGUTGGGGARGGGAGGUTG GGGTGURGGGGAAUUUTUUAGRGUAGRGURGGGAGUUTGXGUTTURGAGGGRGTG RGAGGUTGGUTGGRGGGGGRGGRGUTGTUTGTGTRGGGUUUUAUTGUUTGTAGAGT AAGTGAUTGTUURGGUTRGGGGAGUTUTGURGUUTTUUUTTTUUTUUUTRTAUUUU UURGUUATTTAGTGTUTUAGGGU 403 AUUAUAGUAUTGUAGGAGGATGAGUUUUTGUAGGAAGGAATGUTGGUTUTUTGGG GTAGATAAAGAAGGTTUTGGGGAAGGGAAGGGAGGAAUAGGAAUATGGGUTUUUT GUUAGGUTGTUUUAGGTURGGGATGUUATRGGUAAGTGGGXGGGGAUAGGUUTGG GTAGATGAUATGGTAGTGAGTAAGTGGGGAGGUAGGUUAGUAGAGGAGUUAGGUT UAUUTUUXGUUXGUUUAUUTRGGUUAUAGAURGGGAGGGGTRGGAGUAUTGRGTT GGGGTTGATGAGUAGARGAUTGUUA 404 TGGUAGTRGTUTGUTUATUAAUUUUAARGUAGTGUTURGAUUUUTUURGGTUTGTG GURGAGGTGGGXGGGXGGGAGGTGAGUUTGGUTUUTUTGUTGGUUTGUUTUUUUA UTTAUTUAUTAUUATGTUATUTAUUUAGGUUTGTUUUXGUUUAUTTGURGATGGUA TUURGGAUUTGGGAUAGUUTGGUAGGGAGUUUATGTTUUTGTTUUTUUUTTUUUTT UUUUAGAAUUUUTUTUUATUTAUUUUAGAGAGUUAGUATTUUTTUUTGUAGGGGUTU ATUUTUUTGUAGTGUTGTGGT 405 AGGGAAGGGAGGAAUAGGAAUATGGGUTUUUTGUUAGGUTGTUUUAGGTURGGGA TGUUATRGGUAAGTGGGXGGGGAUAGGUUTGGGTAGATGAUATGGTAGTGAGTAA GTGGGGAGGUAGGUUAGUAGAGGAGUUAGGUTUAUUTUUXGUUXGUUUAUUTRGG UUAUAGAURGGGAGGGGTRGGAGUAUTGRGTTGGGGTTGATGAGUAGARGAUTGU UAGGUAGUUATTUAUAGGAAATGGUAUAGARGUAUATTGTTUUAGUTAUUUUUUA TUUTUUUTUAGGGGUAAAGTGAATG 406 ATTUAUTTTGUUUUTGAGGGAGGATGGGGGGTAGUTGGAAUAATGTGRGTUTGTGU UATTTUUTGTGAATGGUTGUUTGGUAGTRGTUTGUTUATUAAUUUUAARGUAGTGU TURGAUUUUTUURGGTUTGTGGURGAGGTGGGXGGGXGGGAGGTGAGUUTGGUTU UTUTGUTGGUUTGUUTUUUUAUTTAUTUAUTAUUATGTUATUTAUUUAGGUUTGTU UUXGUUUAUTTGURGATGGUATUURGGAUUTGGGAUAGUUTGGUAGGGAGUUUAT GTTUUTGTTUUTUUUTTUUUTT 407 GGTTUTAAAUAUAUAAAUUTTTGATGUATUTGGAATTTAUUTTAATUUUTAUUAAT TTTTATUAATGGUTUAATATTTGGGGGATTTTUATGGTAATTGUAUTGAATGTATTAA UTGGTUAGGGAGGATTAUATUAAGAUUAURGGUTXGAGAAAUAGUAGTUTGTTUUT UUAUUUUUARGTUTGUATUUAGGUUUTTUUAUAGAGATUTUATTTUTUUTGUAGAT GAUTUATTUAGTGTUTAGGAATURGGTGUTUTGTGGUUAUTAURGAGAGTGGGATA TTTTUUUUUATTTTATT 408 AATAAAATGGGGGAAAATATUUUAUTUTRGGTAGTGGUUAUAGAGUAURGGATTUU TAGAUAUTGAATGAGTUATUTGUAGGAGAAATGAGATUTUTGTGGAAGGGUUTGGA TGUAGARGTGGGGGTGGAGGAAUAGAUTGUTGTTTUTXGAGURGGTGGTUTTGATG TAATUUTUUUTGAUUAGTTAATAUATTUAGTGUAATTAUUATGAAAATUUUUUAAA TATTGAGUUATTGATAAAAATTGUTAGGAAATTAAGGTAAATTUUAGATGUATUAA AGGTTTGTGTGTTTAGAAUU 409 TTTGGGGGGUAGGGAGGGTTUAGTUUUUTUAGGUUTGGUTGTGTUUUUTGUUUUUU AUUUAUAATUAGGUUUAGGGTTGGGGGGTGUAUAUUAAGGAGGGGUAGGAAGTGT UUAAGAAGUAGAAURGGUTUTGTGTUUUUAGTGGXGGXGGGTGTUTGGGGUAGGA GGAGGUTATUTGATUUUTTUUUUAUTGUUURGGUUATGAUUTUUTUUUTUUUTUUU TRGUTUUUTUUUTUUTUUUTUUUTUUUTUUUTUUUTUUUTUUTUUUUTTTTUUTU GGGTAGUUAGUAUUUTGGGUTG 410 AGUUUAGGGTGUTGGUTAUUUUAGUUATGAAGGAGGAGGGAGGGAGGGAGGGAG GGAGGGAGGGAGGGAGGGAGRGAGGGAGGGAGGGAGGAGGTUATGGURGGGGUA GTGGGGAAGGGATUAGATAGUUTUUTUUTGUUUUAGAUAUUXGUXGUUAUTGGGG AUAUAGAGURGGTTUTGUTTUTTGGAUAUTTUUTGUUUUTUUTTGGTGTGUAUUUU UUAAUUUTGGGUUTGATTGTGGGTGGGGGGUAGGGGAUAUAGUUAGGUUTGAGGG GAUTGAAUUUTUUUTGUUUUUUAAAG 411 UURGUAAGUUTRGUUUUTUUAGGUUTRGUUUTUUUTUUTTGUAGAGAGTGGUUAA GUTRGTGTTUUAGAGGUTGAATGAGGATTTTGTGRGGAAGUURGAUTATGUTTTGAG UTUTGTGGGTAAGAUURGGAGAUAUTGGAAGAUAGAGAXGUAGAUAGGAAAGAGG UUAAGAUAUTGAUAUAGAUAGAUUUATGUAUUTGAURGGURGAAGAUAGAGUUTR GGAUAGUUUUUAUURGUUUUUAGUUUURGRGUUUURGRGUUURGAUTUURGGUAA GGUUTGGGAGUUTUTGAGGGTTA 412 TAAUUUTUAGAGGUTUUUAGGUUTTGURGGGAGTRGGGGRGRGGGGGRGRGGGGG UTGGGGGRGGGTGGGGGUTGTURGAGGUTUTGTUTTRGGURGGTUAGGTGUATGGG UUTGTUTGTGTUAGTGTUTTGGUUTUTTTUUTGTUTTGGGTTUUUGTAAGRTTT URGGGTUTTAUUUAUAGAGUTUAAAGUATAGTRGGGUTTURGUAUAAAATUUTUAT TUAGUUTUTGGAAUARGAGUTTGGUUAUTUTUTGUAAGGAGGGAGGGRGAGGUUT GGAGGGGRGAGGUTTGRGGG 413 UAGATUAGGGTUUTUAGAUTTGTURGGAGGGAGGGUUUTGUATAUUTGUUAARGU UUTGTTTGUTGGGAAAGGGGUTGATGTTGUAATGAUAGGTTAAAUAGUAAUAGGAU ATTGAUTGGUATUTGUAAGUTGAGUTUAGUTUAGAGAGGXGAGGAGUAUAGGGGA GGGAGGAAAATUURGGTGTGGATUTUAUUUAUARGGUUUAUTGGGTGUTUUTGGU AGARGGAATTATGGGTGUTTTTAUTUTUTUATTTTAAAAATGTGUTTTTTATGTGTAT TGTAAAAGTAAUAGATTUUUA 414 TGGGAATUTGTTAUTTTTAUAATAUAUATAAAAAGUAUATTTTTAAAATGAGAGAGT AAAAGUAUUUATAATTURGTUTGUUAGGAGUAUUUAGTGGGURGTGTGGGTGAGAT UUAUAURGGGATTTTUUTUUUTUUUUTGTGUTUUTXGUUUTUTGAGUTGAGUTUA GUTTGUAGATGUUAGTUAATGTUUTGTTGUTGTTTAAUUTGTUATTGUAAUATUAGU UUUTTTUUUAGUAAAUAGGGRGTTGGUAGGTATGUAGGGUUUTUUUTURGGAUAA GTUTGAGGAUUUTGATUTG 415 UAUTTGGUTUTRGTGGUTGGGAUAGATTGUTTUUTTUUTUTUTUUTGGGTGUUAGGT AGGUUUAGAAAUUAUUTGATGTUAGUAAGGUUTGGUUAUUUAUTGGTGGGGAGGA AGTGGGRGGGTGUUUAGGGAUAGATGAGURGGGUAGAXGTGUUUTGAGGUAGUAU AGTUAGGGUTGARGTGGGUATTATGUAUUTRGGGGUTTTUAGAGUTGGUTURGGTU URGTTTGUUUAUATUAAGUAGGTUAGAGTGGAGAGGGUUAGGGGRGUTGGGGTUA AGGUATGUAUTGAUUAGGRGTU 416 GARGUUTGGTUAGTGUATGUUTTGAUUUUAGRGUUUUTGGUUUTUTUUAUTUTGAU UTGUTTGATGTGGGUAAARGGGAURGGAGUUAGUTUTGAAAGUUURGAGGTGUAT AATGUUUARGTUAGUUUTGAUTGTGUTGUUTUAGGGUAXGTUTGUURGGUTUATUT GTUUUTGGGUAUURGUUUAUTTUUTUUUUAUUAGTGGGTGGUUAGGUUTTGUTGA UATUAGGTGGTTTUTGGGUUTAUUTGGUAUUUAGGAGAGAGGAAGGAAGUAATUT GTUUUAGUUARGAGAGUUAAGTG 417 AUUAUAUTTGAAUATAUAGAUATUUTTTTUUAGGGTGTGTTGTGUTRGATAUUTTT AATTUUTGTUTGUATTUUAGGGUUTGUUUAGUUTUTTUUTGGUTUUUUAGUUUAGU UTGGTUUTTURGGUUTUUUTGTUATUUUUAUUTUTXGTGTGTGUAUAAGUAGGGAU UAGGTAGGGAGAURGGUAGATGUTGUTUTUTGTUUUTGGGGTTTUTTTTUTTAGTGT TGUTUUUAUAUUUARGRGATGUTTTAATTAAUTGUUAUAUTUAGGUTTTUTUAGTG GGGAGAGTUAGAAATAGA 418 UTATTTUTGAUTUTUUUUAUTGAGAAAGUUTGAGTGTGGUAGTTAATTAAAGUATR GRGTGGGTGTGGGAGUAAUAUTAAGAAAAGAAAUUUUAGGGAUAGAGAGUAGUAT UTGURGGTUTUUUTAUUTGGTUUUTGUTTGTGUAUAUAXGAGAGGTGGGGATGAUA GGGAGGURGGAAGGAUUAGGUTGGGUTGGGGAGUUAGGAAGAGGUTGGGUAGGU UUTGGAATGUAGAUAGGAATTAAAGGTATRGAGUAUAAUAUAUUUTGGAAAAGGA TGTUTGTATGTTUAAGTGTGGATG 419 TUUUAGUUAUTURGUAGTUAUTUUTGAUUUAGAAAAGAAUAAUUAUAGUTGGGUU UAGUAUUURGGGUUAUTUUUTGUAGUTGUUUAUAUATUTGGUAGUTGGGTUUAUT TATGUAATGTGGATXGGGTTTTUTTAUATUTGAAATUTGXGTUTUTATUUUTUUTUTG AGAUUAGTGTUTUUTGUUAGUTTUUATGGUUURGGGATGAUUTUAUTUTUUUAGGG TUTUUUTGRGTUUTGGGAGUTUTGGURGAGGAGUAGUAGGGGUTGATGGUAGAGR GGGGGUAGGTUAGAGUTUAGUA 420 GUTGAGUTUTGAUUTGUUUmGUTUTGUUATUAGUUUUTGUTGUTUUTRGGUUAGA GUTUUUAGGARGUAGGGAGAUUUTGGGAGAGTGAGGTUATUURGGGGUUATGGAA GUTGGUAGGAGAUAUTGGTUTUAGAGGAGGGATAGAGAXGUAGATTTUAGATGTA AGAAGUUXGATUUAUATTGUATAAGTGGAUUUAGUTGUUAGATGTGTGGGUAGUT GUAGGGAGTGGUURGGGGTGUUGGGUUUAGUTGTGGTTGTTUTTTTUTGGGTUAGG AGTGAUTGRGGAGTGGUTGGGAU 421 UUAAARGRGGUAUARGGGGARGGUUUUTUURGGGGTUAGGUTUAUTGGUTUUTTU UUTTUAGRGUUAUUAGGUAGGAGGGUUAARGGTUAUAUAGGAGGUAUUUTUAUUT GUUTTTGUAUUAGUAAATAAAGTGUATUUUATTTTXGTGTGAGXGTRGGUURGGTG AGTUAGUUUTTURGGGUUUTTTUUTGTTUTUAGGGUAGGGGGRGTGRGUTGAGUUA GAGGTAGATUTGUAGAAAGGGUUURGAUTGGGUUTRGGGUAGGGURGGRGUUUAU UAUAUTUTGGGGGTUAGUTATGU 422 GUATAGUTGAUUUUUAGAGTGTGGTGGGRGURGGUUUTGUURGAGGUUUAGTRGG GGUUUTTTUTGUAGATTTTAUUTUTGGUTUAGRGUARGUUUUUTGUUUTGAGAAUAG GAAAGGGUURGGAAGGGUTGAUTUAURGGGURGAXGUTUAUAXGAAAATGGGATG UAUTTTATTTGUTGGTGUAAAGGUAGGTGAGGGTGUUTUUTGTGTGAURGTTGGUU UTUUTGUUTGGTGGRGUTGAAGGGAAGGAGUUAGTGAGUUTGAUUURGGGAGGGG URGTUUURGTGTGURGRGTTTGG 423 GUAGGAAGGGUUUAGARGAUAUUUUUAUAGAUATATGUUAGUUUUTURGGGTGAU UAAAATUATUTUAGTAAAGGUAGATGAGGUUAAGRGAAAAGGGGTGGGTGGAAGA AURGGUTUTGAGTUTUAGUUUAUAGAUAUTRGGAUAUTXGTRGGUURGGTAGGUA GGGGTTUUTGGTGGUUTUAGGUTGTUAGGUURGGUUUUUTUURGUAGUTGTUTUUA GUTUUUAUUTUUUURGUUUAUUUUUUAGGAUTUUTATTTUAUTGAGGAGATTAAG AUUAUUTGGRGAGAAUUUUTUUUA 424 GGGAGGGGTTUTRGUUAGGTGGTUTTAATUTUUTUAGTGAAATAGGAGTUUTGGGG GGTGGGRGGGGGAGGTGGGAGUTGGAGAUAGUTGRGGGAGGGGGURGGGUUTGAU AGUUTGAGGUUAUUAGGAAUUUUTGUUTAURGGGURGAXGAGTGTURGAGTGTUT GTGGGUTGAGAUTUAGAGURGGTTUTTUUAUUUAUUUUTTTTRGUTTGGUUTUATU TGUUTTTAUTGAGATGATTTTGGTUAUURGGAGGGGUTGGUATATGTUTGTGGGGGT GTRGTUTGGGUUUTTUUTGUT 425 AGGTGAGATUTGGAGGTTGRGGGGUAGTTAGUAAGTGGGAGAGAGUTGUATGRGGG GAAGGTGGGAGGRGTTGUAGGAAAGGTGAGGGAGAUAUAGUTGAGUTGTGGTGUT GGUUAGUTGGGGUUTTGRGUUTTATURGGGUAUTGTGAXGGUUAUTAAUAGGTTTT AAGTAURGGAATGAUATGATRGGATTTGTAATTTAAUTAGATUUTTUTGAUTGUTGT TGGGGGAAUAGAUTGTUAAUUTUAUAAUAGUAUTGTUAGUTGAGTATTAGAUAAAT GATGAAUUTGGGUUUAGGGA 426 UUUTGGGUUUAGGTTUATUATTTGTUTAATAUTUAGUTGAUAGTGUTGTTGTGAGGT TGAUAGTUTGTTUUUUUAAUAGUAGTUAGAAGGATUTAGTTAAATTAUAAATURGA TUATGTUATTURGGTAUTTAAAAUUTGTTAGTGGUXGTUAUAGTGUURGGATAAGG RGUAAGGUUUUAGUTGGUUAGUAUUAUAGUTUAGUTGTGTUTUUUTUAUUTTTUUT GUAARGUUTUUUAUUTTUUURGUATGUAGUTUTUTUUUAUTTGUTAAUTGUUURGU AAUUTUUAGATUTUAUUTG 427 TGTGTTAUUUUAGAAAGUAAGGARGUTTUUAAAGATGTTUAGAGUAGTGTTUAAAG GGATGUUUAUTGGTUAGTUUUAAURGUTGTGAAUURGGAAAATUTGAGAUTGGTGT UAGTTAATTTAGAAAGTTTATTTTGUUAAGGTTGAGGAXGTATGUUTGTGAUAUAGU UTUAGGAAGTUUTGATGAUATGTGUUUAAGGTGGTTGGGGTGTAGUTTGATTTTATA UAUTTAGGGAGUATGAGAUATUAATTAAGTAUAUTTGAGAAATAUATRGGTTTGGT UTAGAAAGGRGGGAUAAU 428 GTTGTLURGUUTTTUTAGAUUAAAURGATGTATTTUTUAAGTGTAUTTAATTGATGT UTUATGUTUUUTAAGTGTATAAAATUAAGUTAUAUUUUAAUUAUUTTGGGUAUATG TUATUAGGAUTTUUTGAGGUTGTGTUAUAGGUATAXGTUUTUAAUUTTGGUAAAAT AAAUTTTUTAAATTAAUTGAUAUUAGTUTUAGATTTTURGGGTTUAUAGRGGTTGGG AUTGAUUAGTGGGUATUUUTTTGAAUAUTGUTUTGAAUATUTTTGGAAGRGTUUTT GUTTTUTGGGGTAAUAUA 429 TGAGAATAATGTUTGGTATGRGAGGAGUAUUAGUAAATRGTGUTUATUATTUUAGR GGAGUAAATTGTTGUTGTUTUTUAURGGGUTTTGGGTTAUTGAGGUTGUTATTTATT AAAGTGTGGGTTGTGAUTUATTAUTAGGTUATGAAATXGGTGTAGTGGTAGUAAUU AGUUUTTAAAGAAATGAAURGGGGURGGGRGRGGTGGTTUAUAUUTGTAATUUUAG UAUTTTGGGAGGURGAGGRGGGTGGATUARGAGGTUAAGAGATRGAGAUUATUUTG GUUAAUATGGTGAAAUURG 430 RGGGTTTUAUUATGTTGGUUAGGATGGTUTRGATUTUTTGAUUTRGTGATUUAUURG UUTRGGUUTUUUAAAGTGUTGGGATTAUAGGTGTGAAUUAURGRGUURGGUUURG GTTUATTTUTTTAAGGGUTGGTTGUTAUUAUTAUAUXGATTTUATGAUUTAGTAATG AGTUAUAAUUUAUAUTTTAATAAATAGUAGUUTUAGTAAUUUAAAGUURGGTGAG AGAUAGUAAUAATTTGUTURGUTGGAATGATGAGUARGATTTGUTGGTGLTTUUTRG UATAUUAGAUATTATTUTUA 431 AGGATGGAGGURGGGGAGGUAGRGURGURGGRGGGGGRGGGRGGURGRGURGUAG GRGGUTGGGGUAAGTGGGTGRGGUTUAARGTGGGGGGUARGGTGTTUUTGAUUAUU RGGUAGARGUTGTGURGRGAGUAGAAGTUUTTUUTUAGUXGUUTGTGUUAGGGGG AAGAGUTGUAGTRGGAURGGGTGAGGUUUURGGGGTGGGRGGRGAGRGGGRGGTG GGTUUTURGUTRGUURGARGRGGGGUTGTRGGGUUTGGUTRGUURGUUAGGUTGGG GAUURGGURGGGTTUATTTURGA

432 TRGGAAATGAAUURGGURGGGTUUUUAGUUTGGRGGGRGAGUUAGGUURGAUAGU UURGRGTRGGGRGAGRGGAGGAUUUAURGUURGUTRGURGUUUAUUURGGGGGUU TUAUURGGTURGAUTGUAGUTUTTUUUUUTGGUAUAGGXGGUTGAGGAAGGAUTTU TGUTRGRGGUAUAGRGTUTGURGGGTGGTUAGGAAUAURGTGUUUUUUARGTTGAG URGUAUUUAUTTGUUUUAGURGUUTGRGGRGRGGURGUURGUUUURGURGGRGGR GUTGUUTUUURGGUUTUUATUUT 433 TUTAUTGATGRGGAGAURGAGUUUUAGGGUAGUAGAGUUUTAGUTTRGRGUTAUA RGGUTGTGGGRGUTGRGUUUUAGGGUARGGURGGUUUAGGTRGTGGUUUAUTRGG GAUURGRGGUTUAURGGTGRGGTTGARGRGGUARGGGAAGXGGTAGGTGUTUAGU AUUTUUTUUTRGTUUTGUTRGTRGATGAUURGGUAUTGGRGUAGATARGGRGTGAG UTTGGURGGGTTUAGGGRGRGAGUUAGURGATGURGGARGUUUTRGATTRGUTUUU AUAGRGRGTUUTUUTURGUUTUA 434 TGAGGRGGAGGAGGARGRGUTGTGGGAGRGAATRGAGGGRGTURGGUATRGGUTGG UTRGRGUUUTGAAUURGGUUAAGUTUARGURGTATUTGRGUUAGTGURGGGTUATR GARGAGUAGGARGAGGAGGAGGTGUTGAGUAUUTAUXGUTTUURGTGURGRGTUA AURGUAURGGTGAGURGRGGGTUURGAGTGGGUUARGAUUTGGGURGGURGTGUU UTGGGGRGUAGRGUUUAUAGURGTGTAGRGRGAAGUTAGGGUTUTGUTGUUUTGG GGUTRGGTUTURGUATUAGTAGA 435 UTUAUUTTTUUTAGTTTAGAAAATUUUTUAUTGUTTUUUUAATGGAGGUTGUUUUA GGAGTGGUUUAGTGGGGUUAAUUAGUTGTTUTATGUUAGUAGUTURGGAGTATGTA UATTTUUAUTUTGGTTUAAAUTTGTTUTTUTATTUAXGGUUUUATTAAGAAA TUATUTGUAGGUTGGAURGGGTTGGGATGUAGUAAGTTGGTGTGGUTAUTURGAGT GTGTGAUAUAUUTGUAGGGGUUTGTGAGUAGTGGGAGGGUUAGAUATGTGGATTU UUAGGGUTGGTGGUTTUUTT 436 AGGAAGUUAUUAGUUUTGGGAATUUAUATGTUTGGUUUTUUUAUTGUTUAUAGGU UUUTGUAGGTGTGTUAUAUAUTRGGAGTAGUUAUAUUAAUTTGUTGUATUUUAAU URGGTUUAGUUTGUAGATGAATGTTnTUTTAATGGGGUXGTGAATAGAAGAAUAA GTTTGAAUUAGAGTGGAAATGTAUATAUTURGGAGUTGUTGGUATAGAAUAGUTGG TTGGUUUUAUTGGGUUAUTUUTGGGGUAGUUTUUATTGGGGAAGUAGTGAGGGATT TTUTAAAUTAGGAAAGGTGAGA 437 AARGUTGAUATUTTTURGGGTGTUTGAAAAUAGAAUTGGUUTTUUTAAGAAUTAAU AARGATAUTGTTTTUAGUUARGTTUUTTUUTGTTUTTGUTAUARGUTUTGTUAAAT AGGTGGUUAGAGGUURGGGTGUAGATGUAGTGGUTUAXGTUAGTAATUUUAGUAU TUTGGGAGGUTGGTGGGRGGATUAUTTGAGGUUAGGAGTTTAAAGAUUAGUTTGGG UAAUATGGTGAAAUUUTGTUTUTAUTAAAAATAUAAAAAATTAGURGGGTGTGGTG GUAUAAAUUTGTAGTTUUAG 438 UTGGAAUTAUAGGTTTGTGUUAUUAUAUURGGUTAATTTTTTGTATTTTTAGTAGAG AUAGGGTTTUAUUATGTTGUUUAAGUTGGTUTTTAAAUTUUTGGUUTUAAGTGATU RGUUUAUUAGUUTUUUAGAGTGUTGGGATTAUTGAXGTGAGUUAUTGUATUTGUA UURGGGUUTUTGGUUAUUTATTTGAUAGAGRGTGTAGUAAGAAUAGGAAGGGAAR GTGGUTGAAAAUAGTATRGTTGTTAGTTUTTAGGAAGGUUAGTTUTGTTTTUAGAUA UURGGAAAGATGTUAGRGTT 439 GAGGUUUAUUUARGUUUUUAGUTUARGATATUTGUAGAGATGUUAAAUUUTGGUA GAGGAAUTUAGGUUATGTGUTTUAGUUGUTXUUTUAUTUUTUUAUTUUUTGUURGG GUUUTGAGUUAGGAGUUAGGUAUAUAGUTGGAUUUATUXGUUAATGUUAUUUAU UUTTGTGUUUAGUAUURGGUUUARGGUAGGTGUTUAGTGTGUAGGUUUAUATGTA UTAGGTGUAAGGUAARGAUAUAUUAUAUAGGAUAAGGATGUAAAGUAUUTTUTGG GUUUTTUTGRGGUTUTGUUTTUUUA 440 TGGGAAGGUAGAGURGUAGAAGGGUUUAGAAGGTGUTTTGUATUUTTGTUUTGTGT GGTGTGTRGTTGUUTTGUAUUTAGTAUATGTGGGUUTGUAUAUTGAGUAUUTGURG TGGGURGGGTGUTGGGUAUAAGGGTGGGTGGUATTGGXGGATGGGTUUAGUTGTGT GUUTGGUTUUTGGUTUAGGGUURGGGUAGGGAGTGGAGGAGTGAGGGAGUAGUTG AAGUAUATGGUUTGAGTTUUTUTGUUAGGGTTTGGUATUUTGUAGATATRGTGAG UTGGGGGRGTGGGTGGGUUTU 441 GGAGGUAAARGGGAAUURGGUTGGRGGGUTGRGAGURGGTAGGGARGUTGGGGTU UAGGGUTGUTGGAUAGUUURGUUUTGTAUUTUTUUUUATAATTUUUTGGTGGGT GTURGAAATAGUUURGGGTAATUUUAGGGRGAGGUAGTXGGGAATTAAUUUUAGU UTTGAAGTAAGAGAUAGAGGRGTUUAUAGAAGAGGGUTUTGRGRGTUURGGAUTG GAUAUAGRGUAGAGTUUATTUUAGGGAUAURGUAAUURGUAAGRGAUUUAGGUUR GUTUUAGGGRGGGATURGRGRGGU 442 GURGRGRGGATUURGUUUTGGAGRGGGUUTGGGTRGUTTGRGGGTTGRGGTGTUUU TGGAATGGAUTUTGRGUTGTGTUUAGTURGGGARGRGUAGAGUUUTUTTUTGTGGA RGUUTUUXGTUTUTTAUTTUAAGGUTGGGGTTAGTTGGAAUUUTTUUTTTUUGUT TAUURGGGGUTATTTRGGAUUUAGGATTAAGTGAGGGATGGGGAGAGGTAUAGGGR GGGGUTGTUUAGUAGUUUTGGAUUUUAGRGTUUUTAURGGUTRGUAGUURGUUAG URGGGTTUURGTTTGUUTUU 443 UATGTGUTGAGATGGAGAAGGRGUUAGTGTUAGUAUTAGAUAGGUTGAGATGTUA AGTGGAAATGTUAAGGAGGTGGTGGAGGTGGTGGGAGUTGUAGGGUTGTGAGGUU RGGGAGAGGGUUAGAGUTGUAGUTTTAAATTGGAGGGTUAXGGUATGTGGAGGUU AAGGAAGUAGATGGGATGTURGGGGAGAGAGTATGGAUTGAAGUAGUTAAAGAAT TGUAGUATUTAATGGAUAGGAAGAGGGGUAGRGAUAGRGATGGAGUUTGAGAAGG AGGGTGUAGTGTUUUUAAGUUATGT 444 AUATGGUTTGGGGAUAUTGUAUUUTUUTTTTUAGGUTUUATRGUTGTRGUTGUUUU TUTTUUTGTUUATTAGATGUTGUAATTUTTTAGUTGUTTUAGTUUATAUTUUUTUUU RGGAUATUUUATUTGUTTUUTTGGUUTUUAUATGUXGTGAUUUTUUAATTTAAAGU TGUAGUTUTGGUUUUUUURGGGUUTUAUAGUUUTGUAGUTUUUAUUAUUTUUAU UAUTTUUUUUTGAUATTTUUAUTTGAUATUTUAGUUTGTUTAGTGUTGAUAUTGGRGU UTTUTUUATUTUAGUAUATG 445 UUUTUAGGTTTGGTTTUTGTTGURGUTGTTGTTTTUTTTUTUUAAUATUATAAGUUTUT TUUTTATUTTTUUATGTUTGUAUAUAGGAAGRGGUATUAUTTGTTTTTUATGTUUTG RGUATRGAGGUAUAUTTTUUGUTUUTUTTTGTGUXGUUAGURGGUUUAGGUUUAUA GATGGTAGGAUTTGTGUUUUAGGUTGUTGTGTGAGTUAGAGTUAGGUAGGAAGUAA ATGGUAAUTTUAURGRGGTGAUTGAGGAATGUTTAARGAAGGRGURGUUUTTGAUA ARGGTGTGGGTTGGTAA 446 TTAUUAAUUUAUAURGTTGTUAAGGGRGGRGUUTTRGTTAAGUATTUUTUAGTUAU RGRGGTGAAGTTGUUATTTGUTTUUTGUUTGAUTUTGAUTUAUAUAGUAGUUTGGG GUAUAAGTUUTAUUATUTGTGGGUUTGGGURGGUTGGXGGUAUAAAGAGGAGUAG AAAGTGTGUUTRGATGRGUAGGAUATGAAAAAUAAGTGATGURGUTTUUTGTGTGU AGAUATGGAAAGATAAGGAAGAGGUTTATGATGTTGGAAAAGAAAAUAAUAGRGG UAAUAGAAAUUAAAUUTGAGGG 447 TGUTUUTUTTTGTGURGUUAGURGGUUUAGGUUUAUAGATGGTAGGAUTTGTGUUU UAGGUTGUTGTGTGAGTUAGAGTUAGGUAGGAAGUAAATGGUAAUTTUAURGRGGT GAUTGAGGAATGUTTAARGAAGGRGURGUUUTTGAUAAXGGTGTGGGTTGGTAAAA GGAAAUAGURGGGAGUUUTGUAGRGURGGTGURGUUAURGTTTAGTUTGAUTGTGU ATTTGAUTAAGTUAUAAGAGGUUAGGUUTGTGAUTTGTURGAGGGAAAAAUUAUU AGAAAAUUAGGTGTUTGGGUT 448 AGUUUAGAUAUUTGGTTTTUTGGTGGTTTTTUUUTRGGAUAAGTUAUAGGUUTGGU UTUTTGTGAUTTAGTUAAATGUAUAGTUAGAUTAAARGGTGGRGGUAURGGRGUTG UAGGGUTUURGGUTGTTTUUTTTTAUUAAUUUAUAUXGTTGTUAAGGGRGGRGUUT TRGTTAAGUATTUUTUAGTUAURGRGGTGAAGTTGUUATTTGUTTUUTGUUTGAUTU TGAUTUAUAUAGUAGUUTGGGGUAUAAGTUUTAUUATUTGTGGGUUTGGGURGGU TGGRGGUAUAAAGAGGAGUA 449 UTGTGUTUAAGAGUUAUTTUTTAAURGGGGTGGGAGGAAGUAGUTTUAGGAAUTGU TGAGAGAGUAGAAUTUARGUTUUAGGGUTUAGAGUAGGAGGTAGGGTGTGRGGUA AGRGUTGGUURGGAUAGAAGUAGAGTGGGUUUTGGTUTXGGGUAGGATGTTTUTGA UTUAUATTTUUTGAGGAGAGAAAGUTAAGUTUUTGUUTAATGTUTUTGTUTUUUUT TUUAGAAAAATGUUTUAGUTUTTURGGUUTGAAGGAATGGUUTUUTUmGGGUUUU ATGATTUTTTUUTGTGTGGG 450 UUUAUAUAGGAAAGAATUATGGGGUURGGGAGGAGGUUATTUUTTUAGGURGGAA GAGUTGAGGUATTTTTUTGGAAGGGGAGAUAGAGAUATTAGGUAAAGAGUTTAGUT TTUTUTUUTUAGGAAATGTGAGTUAGAAAUATUUTGUUXGAGAUUAGGGUUUAUTU TGUTTUTGTURGGGUUAGRGUTTGURGUAUAUUUTAUUTUUTGUTUTGAGUUUTGG AGRGTGAGTTUTGUTUUTUAGUAGTTUUTGAAGUTGUTC AGAAGTGGUTUTTGAGUAUAG 451 TTTTTTTTTTGAGAUAGAGTUTRGUTUTGTUAUUUAGGUTGGAGTGUAGTGGRGTGA TUTRGGUTUAUTGUAAGUTUUAUUTTUURGGGTTUATGUUATTUTUUTGUUTUAGUT TUUTGAGTATUTGGGAUTAUAGGUAUTUAUUAUUAXGUURGGUTAATTTTUURTTTT TATTTTTAGTGGAGARGGGGTTTUATTGTGTTAGUUAGGATGGTUTRGATUTUUTGA UUTRGTGATUAGUURGUUTUAGUUTUUUAAAGTGUTGGGATTAUAGGTGTGAGUUA UUTUAUURGGUUTGUTA 452 AGUAGGURGGGTGAGGTGGUTUAUAUUTGTAATUUUAGUAUTTTGGGAGGUTGAG GRGGGUTGATUARGAGGTUAGGAGATRGAGAUUATUUTGGUTAAUAUAGTGAAAU UURGTUTUUAUTAAAAATAAAAAAAAAAAATTAGURGGGXGTGGTGGTGAGTGUUT GTAGTUUUAGATAUTUAGGAAGUTGAGGUAGGAGAATGGUATGAAUURGGGAGGT GGAGUTTGUAGTGAGURGAGATUARGUUAUTGUAUTUUAGUUTGGGTGAUAGAGR GAGAUTUTGTUTUAAAAAAAAAAU 453 TTGUUTUTTTTGATTTTTTTUTTTGGGUAGGAGTTAGAATGUAAAATAUAGATTUTAT UTGTATAAAGUAUAUAAGAGATGUTTGGGATUTGGTGATGUTGUAURGGAGATTTU AAUUTGTTTTTUAAAGTGATTUUTAGGGAGTGTGAXGATUTUAAUTUTTTTGGAAGT GAUTTGTUAAAUUATGAGUUATGUTGAGTTUAGUAUAAGTAATATGAGGRGAGGUA AGGUAAGTGGGTGAGTAAGGAGGAAGUAGUUUAGATGAGURGGUAGAGTGUUUAU TGGGAGTGAGGUATGATG 454 ATUATGUUTUAUTUUUAGTGGGUAUTUTGURGGUTUATUTGGGUTGUTTUUTUUTT AUTUAUUUAUTTGUUTTGUUTRGUUTUATATTAUTTGTGUTGAAUTUAGUATGGUTU ATGGTTTGAUAAGTUAUTTUUAAAAGAGTTGAGATXGTUAUAUTUUUTAGGAATUA UTTTGAAAAAUAGGTTGAAATUTURGGTGUAGUATUAUUAGATUUUAAGUATUTUT TGTGTGUTTTATAUAGATAGAATUTGTATTTTGUATTUTAAUTUUTGUUUAAAGAAA AAAATUAAAAGAGGUAAU 455 AUAAGAGATGUTTGGGATUTGGTGATGUTGUAURGGAGATTTUAAUUTGTTTTTUAA AGTGATTUUTAGGGAGTGTGARGATUTUAAUTUTTTTGGAAGTGAUTTGTUAAAUUA TGAGUUATGUTGAGTTUAGUAUAAGTAATATGAGGXGAGGUAAGGUAAGTGGGTG AGTAAGGAGGAAGUAGUUUAGATGAGURGGUAGAGTGUUUAUTGGGAGTGAGGUA TGATGAGGATTAUTRGTRGTGGGAGGUATGAGGGUAUTUTUTGGUAAGGTTUUTTG UATUAUUAAAATGAGGTUAU 456 TGAUUTUATTTTGGTGATGUAAGGAAUUTTGUUAGAGAGTGUUUTUATGUUTUUUA RGARGAGTAATUTTTUATUATGUUTUAUTUUUAGTGGGUAUTUTGURGGUTUATUTG GGUTGUTTUUTUUTTAUTUAUUUAUTTGUUTTGUUTXGUUTUATATTAUTTGTGUTG AAUTUAGUATGGUTUATGGTTTGAUAAGTUAUTTUUAAAAGAGTTGAGATRGTUAU AUTUUUTAGGAATUAUTTTGAAAAAUAGGTTGAAATUTURGGTGUAGUATUAUUAG ATUUUAAGUATUTUTTGTG 457 AGUAAAUAGAGGGTATGGTUUAAUTTGUUTATGAAURGGGAAGUATAATATTTTAA TATTTGTGUUTTAAGUAGTTGTTTTATTTTAAAAGUAUAGGAAATUUTGTUTTTTTU TGTTATAAAATUTTAUAAAGUTAUTGGAAAGATUTUXGUAGGUUAGTGGTTTTUAA AGTGGGTTUUUAGAAUTAGUAAUAGUTGAATUATURGGGAAUTGGTTAGAAATGUA AAGTUTRGURGUUAUUUUTUAAUUUUUUAGAUUTAATGAAUUAGAAATTUTGGGG TGTGGUUUAGTGGUUTGRG 458 RGUAGGUUAUTGGGUUAUAUUUUAGAATTTUTGGTTUATTAGGTUTGGGGGGTTGA GGGGTGGRGGRGAGAUTTTGUATTTUTAAUUAGTTUURGGATGATTUAGUTGTTGUT AGTTUTGGGAATRTUAUTTTGAAAAUUAUTGGUUTGXGGAGATUTTTUUAUTAUUTT TGTAAGATTTTATAAUAAGAAAAAAGAUAGGATTTUUTGTGUTTTTAAGTAAAAUA AUTGUTTAAGGUAUAAATATTAAAATATTATGUTTUURGGTTUATAGGUAAGTTGGA UUATAUUUTUTGTTTGUT 459 GUUUTAUUURGUTUTUTURGAUTUUUURGGGUURGGUUTGRGUUTTUUTGRGGTGU RGAGGAGRGGTGGRGUUUTGGGTGAAGAAGTUURGURGAGTRGAGGGGRGUAATG GAGGAGRGURGGAAUAGGTUTUTUATTURGAGTAGUTAUXGTTGUAUTGTGRGAGT GTAAAAGTUAUTTUUAUURGGTUTUAGTTGTTUUAAUUTUAGTTGAAGTGAGGAGG TTGGAUTGGAAGGTTTUTGGGGTUAUTUUAGTGAGGUTGGGGTTUTAGTUUUAATU TUAURGTGGUAUUUUAAAGGU 460 GUUTTTGGGGTGUUARGGTGAGATTGGGAUTAGAAUUUUAGUUTUAUTGGAGTGAU UUUAGAAAUUTTUUAGTUUAAUUTUUTUAUTTUAAUTGAGGTTGGAAUAAUTGAGA URGGGTGGAAGTGAUTTTTAUAUTRGUAUAGTGUAAXGGTAGUTAUTRGGAATGAG AGAUUTGTTURGGRGUTUUTUUATTGRGUUUUTRGAUTRGGRGGGAUTTUTTUAUU UAGGGRGUUAURGUTUUTRGGUAURGUAGGAAGGRGUAGGURGGGUURGGGGGAG TRGGGGAGAGRGGGGTAGGGU 461 GGAUAUAATUTUTGTTUTTUAAAGTTGGUAUTAAGAGUTUUTUUTGRGGTTUUUUTT UUTUTUUTRGAGUAGUAAAGGRGTGGTUUAUAATGUUUAUUUTGTGGGGTUTAGGG GTGUURGGUTTGUTGAUUTUUAGGUUUUUTUTGTGGXGAGGTTTGGAUTGUATAUA TGGTGUAGGUUUUTUATUAUTGGAGUTGUUAGGAUAGUAUTGGAGAUUUTAAGUU AATAUUTATTTTTGGUAATAATTATUAAGUATTTGTAAAAGUURGGGTATGUTGGUA AATUTTTTTAAAATAAGAG 462 UTUTTATTTTAAAAAGATTTGUUAGUATAUURGGGUTTTTAUAAATGUTTGATAATT ATTGUUAAAAATAGGTATTGGUTTAGGGTUTUUAGTGUTGTUUTGGUAGUTUUAGT GATGAGGGGUUTGUAUUATGTATGUAGTUUAAAUUTXGUUAUAGAGGGGGUUTGG AGGTUAGUAAGURGGGUAUUUUTAGAUUUUAUAGGGTGGGUATTGTGGAUUARGU UTTTGUTGUTRGAGGAGAGGAAGGGGAAURGUAGGAGGAGUTUTTAGTGUUAAUTT TGAAGAAUAGAGATTGTGTUU 463 AUTTGAGRGUTTUTUUAUUUUAGUAGGUURGUTGUUATUAAGGGUTTAUUUTGTGG GUTGUUUARGUTGUTGTAAUUAGTGAUUAUAAGUTURGTGGTGTTGAGAAGUAUAT GTTTUTUUTUUUARGGUTGTGTAGGTURGGAGTUUTAXGGGUTUAGUUAGTUUUUU TGUTUUAGGTTTAAUUAGGURGGAATUAAGATGUUAGGGUUTGGUTGTGUTTTGGA GGUTUTTGGTGAGAAUUTGUTTUTGGUUTGGTGUAGGGTGTGGUAGAATUURGATG UTTGAGTTTGAATGGTGAAA 464 TTTUAUUATTUAAAUTUAAGUATRGGGATTUTGUUAUAUUUTGUAUUAGGUUAGAA GUAGGTTUTUAUUAAGAGUUTUUAAAGUAUAGUUAGGUUUTGGUATUTTGATTUR GGUUTGGTTAAAUUTGGAGUAGGGGGAUTGGUTGAGUUXGTAGGAUTURGGAUUT AUAUAGURGTGGGAGGAGAAAUATGTGUTTUTUAAUAUUARGGAGUTTGTGGTUAU TGGTTAUAGUAGRGTGGGUAGUUUAUAGGGTAAGUUUTTGATGGUAGRGGGUUTG UTGGGGTGGAGAAGRGUTUAAGT 465 AAAUTUARGUTGGUUUAAGAGGAGGAAUAGAGAAGUTTUUTGGUTGAGGUUUAGU RGAUTGUTGAUURGGAAAAGTTTUTRGAGGTGAUTUAUATUUUUAGUUTUTGUAUA TGTGGGTGAGUUAGTTGTAGUTUTGTTUUXGTGAUTGAGUAXGGGAXGURGGAGGT ATTUATUAGGUATGAGGTTATUTGUUTAUTTUUUATGTGTUAGURGAGTGAURGAA TUTUAGTUUUTTAGUUUUTAUATUUUTAGGGTUUTAGTGGAUTGTAAGUTGGTGAT 466 AAGAGTTGTGUTGUUUTUAUT GTGAGGGUAGUAUAAUTUTTATUAUUAGUTTAUAGTUUAUTAGGAUUUTAGGGATG TAGGGGUTAAGGGAUTGAGATTRGGTUAUTRGGUTGAUAUATGGGAAGTAGGUAGA TAAUUTUATGUUTGATGAATAUUTURGGXGTUUXGTGUTUAGTUAXGGGAAUAGAG UTAUAAUTGGUTUAUUUAUATGTGUAGAGGUTGGGGATGTGAGTUAUUTRGAGAA AUTTTTTRGGGTUAGUAGTRGGUTGGGUUTUAGUUAGGAAGUTTUTUTGTTTTUTUU TUTTGGGUUAGRGTGAGTTTT 467 AUTTGAGRGUTTUTUUAUUUUAGUAGGUURGUTGUUATUAAGGGUTTAUUUTGTGG GUTGUUUARGUTGUTGTAAUUAGTGAUUAUAAGUTURGTGGTGTTGAGAAGUAUAT GTTTUTUUTUUUARGGUTGTGTAGGTURGGAGTUUTAXGGGUTUAGUUAGTUUUUU TGUTUUAGGTTTAAUUAGGURGGAATUAAGATGUUAGGGUUTGGUTGTGUTTTGGA GGUTUTTGGTGAGAAUUTGUTTUTGGUUTGGTGUAGGGTGTGGUAGAATUURGATG

UTTGAGTTTGAATGGTGAAA 468 TTTUAUUATUAAAUTUAAGUATRGGGATTUTGUUAUAUUUTGUAUUAGGUUAGAA GUAGGTTTTTAUUAAGAGUUTUUAAAGUAUAGUUAGGUUUTGGUATUTTGATTUR GGUUTGGTTAAAUUTGGAGUAGGGGGAUTGGUTGAGUUXGTAGGAUTURGGAUUT AUAUAGURGTGGGAGGAGAAAUATGTGUTTUTUAAUAUUARGGAGUTTGTGGTUAU TGGTTAUAGUAGRGTGGGUAGUUUAUAGGGTAAGUUUTTGATGGUAGRGGGUUTG UTGGGGTGGAGAAGRGUTUAAGT 469 GRGAATAAAAAGUUAGTGTGTGAGUAAGTUTGTGGGAAGATGUATGUAGAGTGTGA UAGAGAGTTTAGGGGUTRGTGTGAUAATURGTGGAAATGTTTUTAAAGGRGAGGGT ATGTGTGTGGGTGTGAGGAUURGGUTGTTGGATGTTTAXGTATTTTATTAGUTAGAT ARGGGAGUTAATAUTUAATTGUAGTGUAUTAAAUATTATTAGGTGGGTATGATTTTG AGGGAATGAGGGAAGGGAGAUAAGGTUTGGTGAGATUATUTGTGGGATTATUTGTG TGTATTTGUTGGTTTGTA 470 TAUAAAUUAGUAAATAUAUAUAGATAATUUUAUAGATGATUTUAUUAGAUUTTGT TTTUUUTTUUTTTUATTUUUTUAAAATUATAUUUAUUTAATAATGTTUUAAGGU AATTGAGTATTAGUTUURGTATUTAGUTAATAAAATAXGTAAAUATUUAAUAGURG GGTUUTUAUAUUUAUAUAUATAUUUTRGUUTTTAGAAAUATTTUUARGGATTGTUA UARGAGUUUUTAAAUTUTUTGTUAUAUTTTTGUATGUATUTTUUUAUAGAUTTGUTU AUAUAUTGGUTTTTATTRGU 471 UAGTGAGUTGAGAGUARGUUAUTGUAUTUUAGUUTGGGGGATAGAGTGAGAUTUT GTUUUAAAAAAAGAAAAAAAGAAUTGATUUUAAATGTGTGGGGAGAUTGATTTUAG TAATAATAAAAUTURGGTUTUUUAUAUAGTUAGUTUTGXGTGAATUUUTUTTTUUU TATTGRGATTUUUUTGATTTGAGTGAUAGTAAAAUTURGGTUTUUTGUAUAGUUAG UTUTGRGTGAGTUATTUTTTUTUUUUTGTAATTUUUUTGTUTTGATUUATUA GTUTGGGUAGUAGGUAAGGT 472 AUUTTGUUTGUTGUUUAGAUAGAGUTGATGGATUAAGAUAGGGGAATTAUAGGGG AGAAAGAATGAUTUARGUAGAGUTGGUTGTGUAGGAGAURGGAGTTTTAUTGTUAU TUAAATUAGGGGAATRGUAATAGGGAAAGAGGGATTUAXGUAGAGUTGGUTGTGT GGGAGAURGGAGTTTTATTATTAUTGAAATUAGTUTUUUUAUAUATTTGGGATUAGT TUTTTUTTUTUTTUUUGAGAUAGAGTUTUAUTUTATUUUUUAGGUTGGAGTGUAGT GGRGTGUTUTUAGUTUAUTG 473 GGATGTRGGTGTGUUAAUUUUAGUTUUAUUUUAUTGUTAAAGUTTAAGUTUTUUUU TUUUURGTTAAGUTGTATGAUUTTGAGTUUTTGTGUUTUAUTGTUUTUATUTGTUA AGTGAAAATGUTUUUAGTUUUUAUUTURGGGAGTTGXGTGGGAGGUAUAUATGAA UAUUAGGAAAGTGAGTTTATGUAGUURGGGUUAGGGAUTURGGTUTUTGUUTUTGU UUTAATUUUUARGGUUTGGGGGAARGTGUAGGGUTGAGGAAGRGUAGUUTUTUUT TGGAATUTUAGRGGAAGUTUU 474 GGAGUTTURGUTGAGATTUUAAGGAGAGGUTGRGUTUUTUAGUUUTGUARGTTUU UUUAGGURGTGGGGATTAGGGUAGAGGUAGAGAURGGAGTUUUTGGUURGGGUTG UATAAAUTUAUTTTUUTGGTGTTUATGTGTGUUTUUUAXGUAAUTUURGGAGGTGG GGAUTGGGAGUATTTTUAUTTGAUAGATGAGGAUAGTGAGGUAUAAAGAAUTUAA GGTUATAUAGUTTAARGGGGGAGGGGAGAGUTTAAGUnTAGUAGTGGGGTGGAGU TGGGGTTGGUAUAURGAUATUU 475 TAATTGAATUAUATAATTUATTTUUATTATUTGAGTTUURGGUTTAGGUTUTTTGAG TAUUARGAATUAGGAATGAUTATGUTUUAUTTUAUUUTTRGUTAGTUAAAGAUTGU UAGGAGGUURGGGGTTGTGGTATTUAARGTTAUAGAXGTAAGGUUUTUUTGUUUAU UUAGUAUTUUAAATATTTUATGAUATATGAAGGUTUTGAUATTGUAAAURGGAUTA RGAUAAGUUTTTGAUTTTUURGGGTTGTGAGGAGTTTTAGAAAATAAUTGAGAAGU AAUTTTTTTGAGGATGATG 476 UATUATUUTUAAAAAAGTTGUTTUTUAGTTATTTTUTAAAAUTUUTUAUAAUURGGA GAAGTUAAAGGUTTGTRGTAGTURGGTTTGUAATGTUAGAGUUTTUATATGTUATGA AATATTTGGAGTGUTGGGTGGGUAGGAGGGUUTTAXGTUTGTAARGTTGAATAUUA UAAUUURGGGUUTUUTGGUAGTUTTTGAUTAGRGAAGGGTGAAGTGGAGUATAGTU ATTUUTGATTRGTGGTAUTUAAAGAGUUTAAGURGGGAAUTUAGATAATGGAAATG AATTATGTGATTUAATTA 477 UAAUATTUTTGTATUUAGUATUUTTTGTUATGTUATTUTATAGATGUTUTUAUTAA AGTGATGGUUAATTTUUTAUUUTTRGAATURGGGTUTTGGUAAATGGGATGTTAAU AAUAGUTUUUAAAUAGAGGATUAUATAGTAUTTGXGTGAGUUUAUUUUUTUTTAT GTTUTTUAAGUATGUUATGAGAAUAXGUUTGGGTUAGUUTGUTGAAGGAGUTGAGU TGAGTUATUURGGTGAUAGUUAGUTGAUTUTTAGUAGTGAGAGGUAUUUUUAUAA AGUTGUTUTGUTGAUUAUU 478 GTGGTUAGUAGAGUAGUTTTGTGGGGGTGUUTUTUAUTGUTAAGAGTUAGUTGGUT GTUAURGGGATGAUTUAGUTUAGUTUUTTUAGUAGGUTGAUUUAGGXGTGTTUTUA TGGUATGUTTGAAGAAUATAAGAGGGGAGTGGGUTUAXGUAAGTAUTATGTGATUU TUTGTTTGGGAGUTGTTGTTAAUATUUUATTTGUUAAAGUURGGATTRGAAGGGTAA GGAAATTGGUUATUAUTTTAGTGAGAGUATUTATAGAATGAUATGGUAAAGGATGU TGGATAUAAGGAATGTTGU 479 GUTUTUAUTAAAGTGATGGUUAATTTUUTTAUUUTTRGAATURGGGUTTTGGUAAAT GGGATGTTAAUAAUAGUTUUUAAAUAGAGGATUAUATAGTAUTTGXGTGAGUUUA TTTUUUUTUTTATGTTUTTUAAGUATGUUATGAGAAUAXGUUTGGGTUAGUUTGUTG AAGGAGUTGAGUTGAGTUATUURGGTGAUAGUUAGUTGAUTUTTAGUAGTGAGAG GUAUUUUUAUAAAGUTGUTUTGUTGAUUAUUUUAGAUAUARGAGUAAAAGAAATG TTTAUUATTAUATGTUAUTGAG 480 TUAGTGAUATGTAATGGTAAAUATTTUTTTTGUTRGTGTGTUTGGGGTGGTUAGUAG AGUAGUTTTGTGGGGGTGUUTUTUAUTGUTAAGAGTUAGUTGGUTGTUAURGGGAT GAUTUAGUTUAGUTUUTTUAGUAGGUTGAUUUAGGXGTGTTUTUATGGUATGUTTG AAGAAUATAAGAGGGGAGTGGGUTUAXGUAAGTAUTATGTGATUUTUTGTTTGGGA GUTGTTGTTAAUATUUUATTTGUUAAAGUURGGATTRGAAGGGTAAGGAAATTGGU UATUAUTTTAGTGAGAGUA 481 UUUUAGUUAAAUUAUTRGAUTGUUUUUUATUAUUTATAUTGGURGTTTTUUUTGG AGUUTGUAUUUAAUAGTGGUAAUAUUTTGTGGUURGAGUUUUTUTTUAGUTTGGTU AGTGGUUTAGTGAGUATGAUUAAUUUAURGGUUTUUTXGTUUTUAGUAUUATUTU UAGRGGUUTUUTURGUUTURGUUTUUUAGAGUUUAUUUUTGAGUTGRGUAGTGUU ATUUAARGAUAGUAGTUUUATTTAUTUAGRGGUAUUUAUUTTUUUUARGURGAAU AUTGAUATTTTUUUTGAGUUAUA 482 TGTGGUTUAGGGAAAATGTUAGTGTTRGGRGTGGGGAAGGTGGGTGURGUTGAGTA AATGGGAUTGUTGTRGTTGGATGGUAUTGRGUAGUTUAGGGGTGGGUTUTGGGAGG RGGAGGRGGAGGAGGURGUTGGAGATGGTGUTGAGGAXGAGGAGGURGGTGGGTT GGTUATGUTUAUTAGGUUAUTGAUUAAGUTGAAGAGGGGUTRGGGUUAUAAGGTG TTGUUAUTGTTGGGTGUAGGUTUUAGGGAAAAGRGGUUAGTATAGGTGATGGGGGG UAGTRGAGTGGTTTGGUTGGGG 483 GUAGTGGUTGGGUUUUUAUUUUUUAGGAAAUTUAAAAUUUTGGGUUAGURGRGGG TGGRGGGTTGGGGUAGGUAUAAAGAGGGUUTUTGTGRGGURGGUTGGGUTGUUUA UAGGATTUTGGGGGAGGAGGURGGAGURGGTTTUXGTUURGTTUTGUTTUUTGRGG AGGUTGRGGAATGUURGGAGUTUTGGUUUAGUUTGUUURGTUTGGUUUAUURGUA GUUUUTTUUUUATTUUTTTUUAGGGUUTTGGGGTAUAGTUT AGGGUUUTGAGAGUUAUUUTUUA 484 TGGAGGGTGGUTUTUAGGGUUUTGTTGUAGAGAAGTUTGUAGUTGTAUUUUAAGGU UUTGGAAAAGATGGGGAAGGGGUTGRGGGTGGGUUAGARGGGGUAGGUTGGGUUA GAGUTURGGGUATTURGUAGUUTURGUAGGAAGUAGAAXGGGARGGAAAURGGUT URGGUUTUUTUUUUUAGAATUUTGTGGGUAGUUUAGURGGURGUAUAGAGGUUUT UTTTGTGUUTGUUUUAAUURGUUAUURGRGGUTGGUUUAGGGTTTTGAGTTTUUTG GGGGGTGGGGGUUUAGUUAUTGU 485 AGGUAUURGTUAUAARGUURGGUTAATTTTTTTGTATTTTTTAGTAGAGARGGGGTT TUAURGTGTTAGUUAGGATGGTUTUAGTUTUUTGAUUTTGTGATUUAUUUAUUTUA GUUTUUUAAAGTGUTGGGATTAUAGATGTGAGUTAUXGUAUURGGUUAAGTTUATG ATUTTTUTGTAUTUTGAGUUAGTGTTAUTGGUAAAGAATGUUUTGGGUATTGTGGTG TGGATGGAAGUUAGGUAUATTGUATUUATTUUTTUUTAGAUTAAGTTGUUTGGUUT GTGGAUUTTUTUAGUUAG 486 UTGGUTGAGAAGGTUUAUAGGUUAGGUAAUTTAGTUTAGGAAGGAATGGATGUAA TGTGUUTGGUTTUUATUUAUAUUAUAATGUUUAGGGUATTUTTTGUUAGTAAUAUT GGUTUAGAGTAUAGAAAGATUATGAAUTTGGURGGGTGXGGTAGUTUAUATUTGTA ATUUUAGUAUTTTGGGAGGUTGAGGTGGGTGGATUAUAAGGTUAGGAGAUTGAGA UUATUUTGGUTAAUARGGTGAAAUUURGTUTUTAUTAAAAAATAUAAAAAAATTAG URGGGRGTTGTGARGGGTGUUT 487 TTURGTGGGGATGUAAUUTRGTTTGUUUUTUTGAUTTUUUUATGAGATUTUTRGUTT UUTUUUAUAUUTUUTTTATUUUUUAAUUUUUTGURGGTUUAUUAGGUTGUAGUT GGGTUTGRGGGTAGGGGAUATTUUTAGGTUTTGAUXGUUAGAGUAUURGGTUUAGT UURGGUUAUAGUUTTTGGUUUAAGTGAGGGUTGGUUTGGGGAUAAGURGAAATUA GGGUUUTGGUTGTATUUAGAAAGAGAAUTGAGAUURGTTGUUTUUUAUTGGGUUA UUUUURGAUUUUAAUUAUATA 488 ATGTGGTTGGGGTRGGGGGGTGGUUUAGTGGGAGGUAARGGGTUTUAGTTUTUTTT UTGGATAUAGUUAGGGUUUTGATTTRGGUTTGTUUUUAGGUUAGUUUTUAUTTGGG UUAAAGGUTGTGGURGGGAUTGGAURGGGTGUTUTGGXGGTUAAGAUUTAGGAAT GTUUUUTAUURGUAGAUURGUAGUTGUAGUUTGGTGGAURGGUAGGGGGTTGGGG GATAAAGGAGGTGTGGGAGGAAGRGAGAGATUTUATGGGGAAGTUAGAGGGGUAA ARGAGGTTGUATUUUUARGGAAT 489 UTTATAUURGGTUUTRGUUUUTUUAGRGURGGUUTRGUURGRGUTUUTGAGAAAGU UUTGUURGUTURGUTUARGGURGTGUUUTGGUUAAUTTUUTGUTGRGGURGGRGGG UUUTGGGAAGUURGTGUUUUUTTUUUTGUURGGGUUTXGAGGAUTTUUTUTTGGUA GGRGUTGGGGUUUTUTGAGAGUAGGUAGGUURGGUUTTTGTUTURGRGAGGUUUA UUURGGUURGUAUUTTRGUTTTGRGGTUTGAUUUUARGRGUUUUUUTGUAGGGUTG GGUURGGGTGAGGGGAGUTTU 490 GAAGUTUUUUTUAUURGGGUUUAGUUUTGUAGGGGGGRGRGTGGGGTUAGAURGU AAAGRGAAGGTGRGGGURGGGGTGGGUUTRGRGGAGAUAAAGGURGGGUUTGUUT GUTUTUAGAGGGUUUUAGRGUUTGUUAAGAGGAAGTUUTXGAGGUURGGGUAGGG AAGGGGGUARGGGUTTUUUAGGGUURGURGGURGUAGUAGGAAGTTGGUUAGGGU ARGGURGTGAGRGGAGRGGGUAGGGUTTTUTUAGGAGRGRGGGRGAGGURGGRGU TGGAGGGGRGAGGAURGGGTATAAG 491 AGUTUUTTTATUAGAAAGGGUAGURGUAGAGUURGRGTGTGRGRGATGTGGUTGRG GGTGGGGAGRGGGRGGRGGGUURGGGAUAURGRGGUUAUTGTTUTAGUUURGUUT GGGURGUUTGAURGRGGUTURGUTGRGURGUAGUUURGXGUUUUTUTGGUTUUTGT TUURGGGRGRGGGGAGAAGGRGGRGGGGRGRGUUTGGGUURGRGRGGGTGRGAAR GRGAGGTUTTTUUTGGGTGUTUUUAGGTRGGAGGATTUUUAGGGRGGGGGUUATUA GGGTGGRGAGGAAURGGUAGGG 492 UUUTGURGGTTUUTRGUUAUUUTGATGGUUUURGUUUTGGGAATUUTURGAUUTGG GAGUAUUUAGGAAAGAUUTRGRGTTRGUAUURGRGRGGGUUUAGGRGRGUUURGU RGUUTTUTUUURGRGUURGGGAAUAGGAGUUAGAGGGGXGRGGGGUTGRGGRGUA GRGGAGURGRGGTUAGGRGGUUUAGGRGGGGUTAGAAUAGTGGURGRGGTGTUUR GGGUURGURGUURGUTUUUUAUURGUAGUUAUATRGRGUAUARGRGGGUTUTGRG GUTGUUUTTTUTGATAAAGGAGUT 493 TGGAAAAGUUAAUTGTGUAAAUATTRGUTTUTAURGTUAUAAGGTGAAAAGGAAAA ATGUUAAAAAGGAGAGUTTGGAAAUAUAGUAGAAGAGUAATGAUUUUUTGUAGAG AAUATGAAATAAGATURGGUAGTGAUUUUAUTAAAGAUAXGGAAAATAAGGTUUA AUUUAGAAUTGGTUAGAGAAUAUUAUTGTGUTTTAGAGTAAUAATTAUAAAGGAA AAGAGGGATRGGGUAUTGTAATATUURGGGAUTGUAGUTTGTAUTUTUTGGGTGGT GUATTUTGTAATTUAATTAAATU 494 GATTTAATTGAATTAUAGAATGUATTUAUUUAGAGAGTAUAAGUTGUAGTUURGGGA TATTAUAGTGUURGATUUUTUTTTTUUTTTGTAATTGTTAUTUTAAAGUAUAGTGGT GTTUTUTGAUUAGTTUTGGGTTGGAUUTTATTTTUXGTGTUTTTAGTGGGGTTUAUTG URGGATUTTATTTUATGTTUTUTGUAGGGGGTUATTGUTUTTUTGUTGTGTTTUUAA GUTUTUUTTTTTGGUATTTTTUUTUTUTTTTUTTGTGARGGTAGAAGRGAATGTTTGUA UAGTTGGUTTTTUUA 495 UTGUAGATTGAUAUTGTTAATUAUAAAUAAGUUUAGGGTTGTGTTUAGAGAUAAAG TUAGTGTGAURGGTGAUTGTTAUAGUAATAUAAAATAATGGUAGUAGTUUUAUTAG URGAGGUUAGUATRGAATAGGGUAAGTTAUTUAAAUAXGTUAUUUTAGRGAUUAU TUUAAAUAUUTGTGUTTAAAUTAAUTTAGGGAGUURGGTTTTGUAGGATGTGUAAU UARGTTGTGUUUUUTAGGGUTUAUUAGAUTTTAGTAUUTAATGUAGUTAUUUTUAU RGTGGUUUAGGTTUUUAGGGA 496 UUUTGGGAAUUTGGGUUARGGTGAGGGTAGUTGUATTAGGTAUTAAAGTUTGGTGA GUUUTAGGGGGUAUAARGTGGTTGUAUATUUTGUAAAAURGGGUTUUUTAAGTTAG TTTAAGUAUAGGTGTTTGGAGTGGTRGUTAGGGTGAXGTGTTTGAGTAAUTTGUUUT ATTRGATGUTGGUUTRGGUTAGTGGGAUTGUTGUUATTATTTTGTATTGUTGTAAUA GTUAURGGTUAUAUTGAUTTTGTUTUTGAAUAUAAUUUTGGGUTTGTTTGTGATTAA UAGTGTUAATUTGUAGG 467 AAAUAUAGUUAGTUTGTTUTAGUUTUTGTUUTUATTTTUUAUAUUUAGGTTTG UUAGTTUUTTGTUUUAUAGTGATGGGUTTGGGAUTATGGGGTGTUUATTURGGGUTT UUUTGGUTTGUTTAUTTTUTUATGGGTGUTTTGAGXGUUTTTTTUGAGURGGUTUAG GUTTTUUUUUUAUAUUUTITUUTUUUTGUTTUTATUAGGUUAAGGGTTTAGATTT TRGGTUAGTGAGTUATUUAAAUUTGGGTGTGGAAAGUAUUTGGGAUAUUAUTTGTA TTTGGUTUUTTTTAGUT 498 AGUTAAAAGGAGUUAAATAUAAGTGGTGTUUUAGGTGUTTTUUAUAUUUAGGTTTG GATGAUTUAUTGAURGAAGUTUTGAUUUTUAUTGUUAGATAGAAGUAGGGAGGAA AGGGTGTGGGGGGAAAGUUTGAGURGGUTUAAAAAAGGXGUTUAAAGUAUUUATG AGAAAGTAAGUAAGUUAGGGAAGUURGGAATGGAUAUUUUATAGTUUUAAGUUUA TUAUTGTGGGAUAAGGAAUTGGAGUAAAGGGAAGGGGGAAGAAAATGAGGAUAGA GGUTAGAAUAGAUTGGUTGTGTTT 499 GTUUUUAAAGGUTGAAUUTTTGATUAATGUAGUUUAAGUTGUARGGGUAGAGAAA GGGTGRGGGGTAGGGGURGGGGTTGGGRGUTGAGUTUUTUTGAAURGGTTGUUAGG UAAUAGAATGGAAATTUARGGGRGGUTAAATGGAGUTUXGUUAUAAATGTTUTGTG GUAAAUURGGAUUUAGTUAUATRGUUUTTTUUUUUUUUUTUUUTTTUUUGGGGUT TUTUATUTGTAAATGAGAAGGGTGUAGAGAAGAUTUTTTTUTTRGGAGTUAGTGUUT URGGTTTGUAUTGUTTTTUA 500 TGAAAAGUAGTGUAAAURGGAGGUAUTGAUTURGAAGAAAAGAGTUTTUTUTGUA UUUTTUTUATTTAUAGATGAGAAAAUTUAGTGGGGTGGGAGGGGGGAGAAAGGGR GATGTGAUTGGGTURGGGTTTGUUAUAGAAUATTTGTGGXGGAGUTUUATTTAGUR GUURGTGAATTTUUATTUTGTTGUUTGGUAAURGGTTUAGAGGAGUTUAGRGUUUA AUUURGGUUUUTAUUURGUAUUUTTTUUTGUURGTGUAGUTTGGGUUGGUUUUAGG UAAAGGTTUAGUUTTTGGGGAU 501 UTUUAURGURGGUTRGUUUUUTGAGGAGGGGGUTGGGUUAGGGUUTRGGUTGAUR GGGGAGGAAGAAGGGGAGUAGAGAAAAAUATGAGTUAUAGURGTGTGTUAUTGGA GRGUATTTUAATTUUUTGUATUAUAGGAGGTGTGGAAGGUXGUUTRGGGGAURGGG RGRGGGAGGTGRGUURGAGAAGGUUURGGGURGGUUTGUAGGGRGRGURGUTURG UUTGRGUUUTTTUUTUUUTAURGUUUTUUURGUUATUTTUUUUTTTGGUTTUUTTU TRGUTRGGTGUAAUAAGTUTTT 502 AAAGAUTTGTTGUAURGAGRGAGAAGGAAGUUAAAGGGGAAGATGGRGGGGAGGG RGGTGGGGGAGGAAAGGGRGUAGGRGGAGRGGRGRGUUUTGUAGGURGGUURGGG GUUTTUTRGGGRGUATUTUURGRGUURGGTUUURGAGGXRGGUUTTUUAUAUUTUU TGTGATGUAGGGAATTGAAATGRGUTUUAGTGAUAUARGGUTGTGAUTUATGTTTTT UTUTGUTUUUUTTUTTUUTUUURGGTUAGURGAGGUUUTGGUUUAGUUUUUTUUTU AGGGGGRGAGURGGRGGTGGAG 503 UUTGAAGAGUATTUTUUUTGAGTGUTUAATGATATGUUAGAGUATGTUTUAAATGR GGAGGATGGGGAGGURGGUTUUUTGGUAGATUTTUATGGAGAAGUTGAUTUUAGU RGGUTTGTGTGUURGTUUUAGAGGAGRGGAAAUAGAGUXGAAGUUUAUAUUUUUA GGGUUUAGGUUUAGUUUTTUUAAGTURGGAGUTUAUUUAGUUTGUUUUTRGGUTU

UTTUATUUTUUTUUAGAUAURGTUUUTTUTTUTGTUTUTGUATTTUUUATUUTUTUR GUUUUTUUUTGTGUTGUTUTGT 504 AUAGAGUAGUAUAGGGAGGGGRGGAGAGGATGGGAAATGUAGAGAUAGAAGAAG GGARGGTGTUTGGAGGAGGATGAAGGAGURGAGGGGUAGGUTGGGTGAGUTURGG AUTTGGAAGGGUTGGGUUTGGGUUUTGGGGGTGTGGGUTTXGGUTUTGTTTURGUT UUTUTGGGARGGGUAUAUAAGURGGUTGGAGTUAGUTTUTUUATGAAGATUTGUUA GGGAGURGGUUTUUUUATUUTURGUATTTGAGAUATGUTUTGGUATATUATTGAGU AUTUAGGGAGAATGUTUTTUAGG 505 ATGTUTGGGAGGUUAAAAGUATUTUTUAGAUAGTUTUTAUAGGAUTUTTUUAGGTU URGGAAGUURGAGRGAGUTTUUTGGAGGAGGTGGUTGGGGAGAGTGGAGGAGURG GTAGGGGTRGUTGTGUTTGRGRGRGUURGTUUAGGAAUTXGURGGGGUTGTGGGGA GGGGGRGURGGUUTGGAGAGGAUAATGTAUAGTUTGTTUTAAUAUUUAUUUAUTU UAAARGUAUAUTTUUUAUUURGTUTUTTGTUUUTUUUAGUUURGGGGUTAGAUUUT GAGGGUTRGGGURGUAUUTUAU 506 GTGAGGTGRGGUURGAGUUUTUAGGGTUTAGUUURGGGGUTGGGAGGGAUAAGAG ARGGGGTGGGAAGTGTGRGTTTGGAGTGGGTGGGTGTTAGAAUAGAUTGTAUATTG TUUTUTUUAGGURGGRGUUUUUTUUUUAUAGUUURGGXGAGTTUUTGGARGGGRG RGRGUAAGUAUAGRGAUUUUTAURGGUTUUTUUAUTUTUUUUAGUUAUUTUUTUU AGGAAGUTRGUTRGGGUTTURGGGAUUTGGAAGAGTUUTGTAGAGAUTGTUTGAGA GATGUTTTTGGUUTUUUAGAUAT 507 GGAGRGUTAARGRGUAGTGGGAGGGAAGGAGAGGAUTGAAGAGAGARGGGGGAGG GGAGAGGAGGGGTRGGUTGUUAGGUUTAGGTGGGGTGAATURGUAGUTGGGUTGA UTUAAGRGGAGGAGURGGAAGGAUAUUURGRGAGGUTTXGGGGRGRGUTTTTAGG GAGGRGURGUUTUUAGUTTTGTGUUAGAAAGTGGGGGTTGRGGUTUAGGUTTGAAT UUAAGAAAGGUTURGGGTGGAAUTUUTGGGUAUUTTGGGTUUTTAUTTTGUUTTUA GGRGUTGGUUAURGTTGGGAUTT 508 AGTUUUAARGGTGGUUAGRGUUTGAAGGUAGAGTAAGGAUUUAGGGTGUUUAGGA GTTUUAUURGGAGUUTTTUTTGGATTUAAGUUTGAGURGUAAUUUUUAUUGGTT UAUAAAGUTGGAGGRGGRGUUTUUUTAAAAGRGRGUUUXGAAGUUTRGRGGGGTG TUUTTURGGUTUUTURGUTTGAGTUAGUUUAGUTGRGGATTUAUUUUAUUTAGGUU TGGUAGURGAUUUUTUUTUTUUUUTUUUURGTUTUTUTTUAGTUUTUTUUTT UUUAUTGRGRGTTAGRGUTUUU 509 TATUAGAATUUAUATAUUUAGGTGGGTTTAGGAUUTUTAGGUUTUTUUUTUAGGU UATAGGAGUAUUUAUUURGGGUTLTUTUTGGAGGGGUAGUUUUAAGGAAUUTGTTG GGGTAAUTTGTTTGUTUUUUAUAUUURGGGAATGTGUXGTUUTTTUAGGUURGUUU AUURGGATTUUTGTGUAGGGAGTUAGURGAUAUAGUATGTTGUATGTGUUUTGTGG GGAUARGTTUTGUUTUUTGTUAGGGGGAGGAGGUTGGRGGURGTGUUTGTGUTGUR GUAUUTUAGUTUUUUAURGAA 510 TRGGTGGGGAGUTGAGGTGRGGUAGUAUAGGUARGGURGUUAGUUTUUTUUUUUT GAUAGGAGGUAGAARGTGTUUUUAUAGGGUAUATGUAAUATGUTGTGTRGGUTGA UTUUUTGUAUAGGAATURGGGTGGGRGGGUUTGAAAGGAXGGUAUATTUURGGGG TGTGGGGAGUAAAUAAGTTAUUUUAAUAGGTTUUTTGGGGUTGUUUUTUUAGAGG AGUURGGGGTGGGTGUTUUTATGGUUTGAGGGAGAGGUUTAGAAAGTUUTAAAUU UAUUTGGGTATGTGGATTUTGATAU 511 AGAGGATTTAAGAUTUAUUUAGGGUAAAUAUTGGGAUUAUTGTAAGAGRGUTGGA AUATTUTGUUTUTTGAGTGAAGGGGUUTTUTTTUTAGUUTUTATGGUAUTGAGGGGT GRGURGGUTGGTGGAGGAGUAGTURGATGGAGUUUTGXGTTUUURGGGGAUAUAG GGUUAAGUTTTGAGGTGGAAAGTTTUTGGTTUTGAAAUAAUAAGGAGAGAGTUTGT TTTTUTTUUTAAAATTTGGAUTUTTGTUTGUAUAAAUTUTGGTUTGTTTTGUARGGTT TGTGTGUUTTTTTTTUUUT 512 GGGAAAAAAAGGUAUAUAAAURGTGUAAAAUAGAUUAGAGTTTGTGUAGAUAAGA GTUUAAATTTTAGGAAGAAAAAUAGAUTUTUTUUTTGTTGTTTUAGAAUUAGAAAU TTTUUAUUTUAAAGUTTGGUUUTGTGTUUURGGGGAAXGUAGGGUTUUATRGGAUT GUTUUTUUAUUAGURGGRGUAUUUUTUAGTGUUATAGAGGUTAGAAAGAAGGUUU UTTUAUTUAAGAGGUAGAATGTTUUAGRGUTUTTAUAGTGGTUUUAGTGTTTGUUU TGGGTGAGTUTTAAATUUTUTT 513 TGUUTUTGAGTUTAAAARGGUAGTGGUUTAGGAGUAUAGGGUUTGGGGUUAUGGU UAGTGUUAUAUUTAAUUTGAGATATGTUUAGAGUTGAGGTUTAGUTUAUAGUATUT GTGRGTRGGGGAAGUTGGUTGRGGTUARGGURGGTGUAGXGGUUUAAGGAGTUUA UAAAGUAGTAAUUTTGGUUUAUAUUAUAGUTURGGTGUATTTGGAGAGGGGGUUU AGTUTAGGUTGAAGTTGGGGGGAGUUTGGUUAGGGUUTGGGUAUUAGGRGUAGGA UAGAGGGAAAGGUUTUUAGUTUUT 514 AGGAGUTGGAGGUUTTTUUUTUTGTUUTGRGUUTGGTGUUUAGGUUUTGGUUAGGU TUUUUUUAAUTTUAGUUTAGAUTGGGUUUUUTUTUUAAATGUAURGGAGUTGTGGT GTGGGUUAAGGTTAUTGUTTTGTGGAUTUUTTGGGUXGUTGUAURGGURGTGAURG UAGUUAGUTTUUURGARGUAUAGATGUTGTGAGUTAGAUUTUAGUTUTGGAUATAT UTUAGGTTAGGTGTGGUAUTGUUUUTGUUUUUAGGUUUTGTGUTUUTAGGUUAUTG URGTTTTAGAUTUAGAGGUA 515 GUAGUUUTGGGGRGTGGGGGGRGGUTGTTTUUTGUTGUUUUTTGGGUTGUUAUUTG UURGAGUTGUUAGUUAUAGTTGGAUTTUUTTUUAGUUUTURGGGGTGUUTGUATTU UUAUATTRGAGAUAGGUAGTGAGAGGGAGTGAGGGGXGATGATGTUTGUAGUUUA UAAGAGUUTURGGGUAGTAGUUAGGUUUUTUUGUTUAGUUTGAUUTGUUTGGUUT UUAGUAGGGTGUTATGGUUUTGGGAGGUUUTGGUTTUTCGGGAATTTGUUTTUUU UUUTGRGUTUTGUTUTGUTGTG 516 AUAGUAGAGUAGAGRGUAGGGUAGGGGAGGAAAGGGGGUAGAAGUUAGGGUUTU UUAGGGUUATAGUAUUUTGUTGGAGGUUAGGUAGGTUAGGUTGAGUAGAGGGGUU TGGUTAUTGUURGGAGGUTUTGTGGGUTGUAGAUATUATXGUUUUTUAUTUUUTU TUAUTGUUTGTUTRGAATGTGGGAATGUAGGUAUUURGGAGGGUTGGAAGGAAGTU UAAUTGTGGUTGGUAGUTRGGGUAGGTGGUAGUUUAAGGGGUAGUAGGAAAUAGU RGUUUUUUARGUUUUAGGGUTGUU 517 TUTUTUUTGGGUUAAGUTTTGTGGATGUUUAGUUTGGGGURGRGGGGAGUTGGUAG GTUAGTGGUAGAUAUTGGTGGGUAGAUUTAGTGTUTGGTAGAAUAGGUATUAAGG AAGTGGTGAURGGAGGGAAGUUAAGTGUAUTUAAAUUUTXGGGTGAGTUATUAUR GURGGGTUTTTUAUAGUTGUTGAAAGTGAGUAAUAGTGATGAAGGTTTGTGAGTTT UTGRGTGAGRGAGTGAATGGAUUAGTAGUAGTTTUUAGGTTGTGGAAGAGRGTTUU UTUUURGGGATGGGGAUAUTTG 518 UAAGTGTUUUUATUURGGGGAGGGAARGUTUTTUUAUAAUUTGGAAAUTGUTAUTG GTUUATTUAUTRGUTUARGUAGAAATTTUAUAAAUUTTUATUAUTGTTGUTUAUTTT UAGUAGUTGTGAAAGAUURGGRGGTGATGAUTUAUUXGAGGGTTTGAGTGUAUTTG GUTTUUUTURGGTUAUUAUTTUUTTGATGUUTGTTUTAUUAGAUAUTAGGTUTGUU UAUUAGTGTUTGUUAUTGAUUTGUUAGUTUUURGRGGUUUUAGGUTGGGUATUUA UAAAGUTTGGUUUAGGAGAGA 519 GGUTGGTUTTGAAUTUUTGGGUTUAAGAGUTUUAUUTGUUTUAGUUTUUUAAAGTG AGUUAUUAGGUUTAUURGGTUUTTTUUTUUATGUTTUTGTGGUUTTTUUTUUTGTT TAGXGAGUTUTGAUATTUAUTUATAGGTAGGAAUAAAGUUUTUUATTGGTTAGTUT GGGUTGAGGTGGGXGTGTGTGTTTUTGTATUAGTGATUTGTTTTURGGUAGGUUTUT UUUTGAGGGGAGAGUTGGTAGUTTUUATGTAAGTGGUAGGGUATAUTTUAUTAAAT AAAAGATGTGTGGGTGAG 520 UTUAUUUAUAUATUTTTTATTTAGTGAAGTATGUUUTGUUAUTTAUATGGAAGUTA UUAGUTUTUUUUTUAGGGAGAGGUUTGURGGAAAAUAGATUAUTGATAUAGAAAU AUAUAXGUUUAUUTUAGUUUAGAUTAAUUAATGGAGGGTTTTTGTTUUTAUUTATGA GTGAATGTUAGAGUTXGUTAAAUAGGAGGAAAGGUUAUAGAAGUATGGAGGAAAA GGAURGGGTAGGUUTGGTGGUTUATTTTGGGAGGUTGAGGUAGGTGGAGUTUTTGA GUUUAGGAGTTUAAGAUUAGUU 521 UAAGUATUTTAGTGATGTGAGTUATUAAAAUTTUUTUUTGGGTUTGUTTTGAGUUU UAUUTTUUTUUTUUTGUAGTUATGTTTUTTAGUUTUAGGGUUUTGGGGRGGAR GGAUAUTUUUUUAGUAGUUTGUTTTUUAGAGGUUAUTGXGUTGUTUAGUTURGGG GGUURGTUUTURGTGGATUUUTUUAGGUUUAGUAGAGTGTTTGAUUARGGGUUTGA URGGGAGGGGAGARGUUAUUTUUTGGGGAUTTGUAUUUUAAUUAGUAUUAUTGTU ATGAGAUAUURGGAGGUUAGUA 522 TGUTGGUUTURGGGTGTUTUATGAUAGTGGTGUTGGTTGGGGTGUAAGTUUUUAGG AGGTGGRGTUTUUUUTUURGGTUAGGUURGTGGTUAAAUAUTUTGUTGGGUUTGGA GGGATUUARGGAGGARGGGUUUURGGAGUTGAGUAGXGUAGTGGUUTUTGGAAAG UAGGUTGUTGGGGGAGTGTURGGGRGTURGUUUUAGGGUUUTGAGGUTAAGAGUA TGAUTGUAGGAGGAGGAAGGTGGGGUTUAAAGUAGAUUUAGGAGGAAGTTTTGAT GAUTUAUATUAUTAAGATGUTTG 523 TGATGAUUAGGUAUTGUTATTUTTTAGGURGGGATTTUUUUAAGUUTTGGTATTTTT AAAAATARGTTATAGTTUUUTTGAAAUTUTUTUUTTATUAUUTUUAUUTTGTTT TUATUTUUUAUTUUTTGGUAUUUTUTGTUTUUUUAXGGTGTUUUUATGARGUTGUU TGUATGUUUATTGGUUUUAGUUTGGGAGUTTUTUAGAGARGUURGGGUUAGAUAT GGUTGUAGATAGAGUUAAGAGGGTGGUUTRGGGTGGUTGGTGGUAGTUTUUTGGUT GTGGGGGUAGAAGTGGGGG 524 UUUUUAUTTUTGUUUUUAUAGUUAGGAGAUTGUUAUUAGUUAUURGAGGUUAUUU TUTTGGUTUTATUTGUAGUUATGTUTGGUURGGGRGTUTUTGAGAAGUTUUUAGGU TGGGGUUAATGGGUATGUAGGUAGRGTUATGGGGAUAUXGTGGGGAGAUAGAGGG TGUUAAGGAGTGGGAGATGAAAAUAGGAAGGTGGAGGTGATAAGGAGAGAGTTTU AAGGGAAUTATAARGTATTTTTAAAAATAUUAAGGUTTGGGGAAATUURGGUUTAA AGAATAGUAGTGUUTGGTUATUA 525 GUUTAGUUURGRGRGUAUATAUARGTGTGUTUTURGRGRGGAUUTRGGGAAUTTTG UUUTUARGUURGRGGRGRGUTTGUUTUURGUURGUUURGGUUTUUAUUUUTGGT ATGUUUUTTUUUUAGURGGTUTUUUUTUUUUURGGUTXGGGAAGAAGUUTGUTGG GUUAGGGRGUUUTGAUUAUUTUUTRGGAGGURGGUAAAUUTGUUTGAAURGUUUU AGAGGAATRGGGUAGGGGUTRGUAUUUUAUUURGGUAGGAGGGUUURGAGAURGA UURGGGURGGGGUTURGUAGURG 526 RGGUTGRGGAGUUURGGUURGGGTRGGTUTRGGGGUUUTUUTGURGGGGTGGGGTG RGAGUUUUTGUURGATTUUTUTGGGGRGGTTUAGGUAGGTTTGURGGUUTURGAGG AGGTGGTUAGGGRGUUUTGGUUUAGUAGGUTTUTTUUXGAGURGGGGGGAGGGGA GAURGGUTGGGGAAGGGGUATUTRGAAGGGGTGGAGGURGGGGRGGGRGGGAGGU AAGRGRGURGRGGGRGTGAGGGUAAAGTTUURGAGGTURGRGRGGAGAGUAUARG TGTATGTGRGRGRGGGGUTAGGU 527 GAAARGGRGGTRGUAGUUUTRGGURGGGUARGRGTGGGGURGTTRGTGGAGRGGTG TUTTGUTAGGURGGTTGGGGTAUTTGRGGGGURGGATGGGUTTGAGGGTGAGXGGR GGUTGGGGUAGGUTGUUAAAGUURGGGTGGATUTGUTTGTUTTTGAATGUUTTGAT GGTUTUUAGAGGGGTAATAGGGGGXGGGTTGAUURGGATGGGGTUUATGUUUTGG AAGGGUTTGTGUTURGGAATGGAGUUUATGTRGTTGGGGTGGTGGTAGAGGTTGTA GTUAGGAATUATGGGGAAGAG 528 UTUTTUUUUATGATTUUTGAUTAUAAUUTUTAUUAUUAUUUUAARGAUATGGGUTU UATTURGGAGUAUAAGUUUTTUUAGGGUATGGAUUUUATURGGGTUAAUUXGUUU UUTATTAUUUUTUTGGAGAUUATUAAGGUATTUAAAGAUAAGUAGATUUAUURGG GUTTTGGUAGUUTGUUUUAGURGURXGUTUAUUUTUAAGUUUATURGGUUURGUA AGTAUUUUAAURGGUUTAGUAAGAUAURGUTUUARGAARGGUUUUARGRGTGUUR GGURGAGGGUTGRGAURGURGTTTU 529 TGUTUAGGUTGGAGTGUAGTGGUAAAATUTTGGUTUAUTTUAAUUTURGUUTUURG GGTTUAAGUAATTUTUUTGUUTUAGUUTUTUAAGTAGUTGGGATTAUAGGUATGUA UUATUAUAUUUAGUTGATTTTGTATTTTTAGTAGAGAXGGGGTTTUAUUARGTTGTT UAAGUTGGTUTUAAAUTUUUTGAUUTUAGGTGATUUAUURGUUTTGGUUTUUUAAAG TGURGGGATTATAGGTGTGAGUUAURGUAUUTGGGUAATTAGTATTGTATTTAAGA GTTTATATTUATATUUATA 530 TATGGATATGAATATAAAUTUTTAAATAUAATAUTAATTGUUUAGGTGRGGTGGUTU AUAUUTATAATUURGGUAUTTTGGGAGGUUAAGGRGGGTGGATUAUUTGAGGTUAG GAGTTTGAGAUUAGUTTGAAUAARGTGGTGAAAUUUXGTUTUTAUTAAAAATAUAA AATUAGUTGGGTGTGATGGTGUATGUUTGTAATUUUAGUTAUTTGAGAGGUTGAGG UAGGAGAATTGUTTGAAUURGGGAGGRGGAGGTTGAAGTGAGUUAAGATTTTGUUA UTGUAUTUUAGUUTGGGUA 531 TGTTAUTTUATTGAATTUTUATAATAGUTTAATGUTATRGGTTTTUTTUTTAATTTTG GGGGUATAGTGGGGAGATAAGUAAAUTGATAUUURGGAGGTTGAGTGAUTUATTUA TGGAATGUAGUAGGUURGTGAGTUAAAGXGAGTAUATGGUAAGAUXGAGTGAAGU TGGGGAAUAATAGUUAAGUUAAGAGRGTTTTAAAGATAUTTAGUATUTTUATUAUA UTGAATUTTTAAGGTGAUAGUAUTTUUAUTRGAUAGUAAAATGTUAGATTUAAUTGT TTUTTTURGGTUTTUAAAU 532 GTTTGAAGAURGGAAAGAAAUAGTTGAATUTGAUATTTTGUTGTRGAGTGGAAGTG UTGTUAUUTTAGGATTUAGTGTGATGAAGATGUTAAGTATUTTTAAAARGUTUTTGG UTTGGUTATTGTTUUUUAGUTTUAUTXGGTUTTGUUATGTAUTXGUTTTGAUTUARG GGUUTGUTGUATTUUATGAATGAGTUAUTUAAUUTURGGGGTATUAGTTTGUTTATU TUUUUAUTATGUUUUUAAAATTAAGAAGAAAAURGATAGUATTAAGUTATTATGAG AATTUAATGAAGTAAUA 533 TTAGTATTAUUAAATATRGAGTUAAGGGUUTGATUAGUUUUAAAAGAATGAGGUAU TTTTAATGTGAUAUUATTUUTGGUAGTUTUAGGTTRGGUTUUUUUAGGUUURGGAT GUAGATGGUTGTTAGGGGUTGGUUATUUTUATUTUAAXGGTUUTGGAAGGUAUUAU TTTUAGGGUATATGUUATGAUTAAUATTURGGTGAGUAATGUTGAUTUAATRGTAG AUTGTTATTTUATGTTUUUAGTAUUUTGTGUAGGAAGGGAAGGGAAATGAGTAATA GATGTATUAGTUUUATTUAA 534 TTGAATGGGAUTGATAUATUTATTAUTUATTTUUUTTUUUTTUUTGUAUAGGGTAUT GGGAAUATGAAATAAUAGTUTARGATTGAGTUAGUATTGUTUAURGGAATGTTAGT UATGGUATATGUUUTGAAAGTGGTGUUTTUUAGGAUXGTTGAGATGAGGATGGUUA GUUUUTAAUAGUUATUTGUATURGGGGUUTGGGAGAGURGAAUUTGAGAUTGUUA GGAATGGTGTUAUATTAAAAGTGUUTUATTUTTTTGGGGUTGATUAGGUUUTTGAUT RGATATTTGGTAATAUTAA 535 AGTGGTGGUTGUTGTTTUTRGGTGGUAGAGATGATGUUTGGTTTATTUTTAGTAAAG TGUTTAGGARGUTGAGUUTGAGGGGUTUTGGAATGGAAAAAUAAAAUAAAAUAAA AUAAAURGGAGGUURGUTUTGUUTGGUTUUTAGAGAUAXGUAAAGUTGGGUAAAG GAAGGAGATTGAGGTGGGAUTGAGAUATTGTTGUATTGTGAATGUUURGGTTUUUU AUUTUUTGUUUUURGAATUATGATTGTTTTATGRGGTTATTTTTUUUTTTGGTGAGG AAAATGGGATGTGGTGTUAA 536 TTGAUAUUAUATUUUATTTTUUTUAUUAAAGGGAAAAATAAURGUATAAAAUAATU ATGATTRGGGGGGUAGGAGGTGGGGAAURGGGGUATTUAUAATGUAAUAATGTUTU AGTUUUAUUTUAATTTTUUTTUUTTGUUUAGUTTTGXGTGTTUUUTAGGAGUUAG AGAGRGGGUUTURGGTTTGTTTTGTTTTGTTTTGTTTTTUGATTGGTTGGAAGGTT GUTUAGRGTUUTAAGUAUTTTAUTAAGAATAAAUUAGGUATUATUTUTGUUAURGA GAAAUAGUAGUUAUUAUT 537 GGGGTRGGUATGGGUTGGAGUTUAGAGARGGUUAGUTAGGAUTTUAGGAUAUAUA GUAAAUTAGUTGRGUUURGUTGAGGGTUAGRGUAUAGURGUUUAUAUAAGGTGTU UTUTUUURGGGUTUTUTGGGURGURGGUUTUUTGUTTUUXGTGURGUAGAURGGGA TTAGAUTGTGGARGRGGGGAAGGAAGGGGGRGTTGRGARGGGATUTTGAGGGGAGU AGGAUTTGUUUUTGUUUUTGRGGRGAAGUTUTAGGUUUTGGUAAGGTTRGGTAUAU RGGGGGURGUTUUTUUUUAGGG 538 UUUTGGGGAGGAGRGGUUUURGGTGTAURGAAUUTTGUUAGGGUUTAGAGUTTRG URGUAGGGGUAGGGGUAAGTUUTGUTUUUUTUAAGATUURGTRGUAARGUUUUUT TUUTTUUURGRGTUUAUAGTUTAATUURGGTUTGRGGUAXGGGAAGUAGGAGGURG GRGGUUUAGAGAGUURGGGGAGAGGAUAUUTTGTGTGGGRGGUTGTGRGUTGAUU UTUAGRGGGGRGUAGUTAGTTTGUTGTGTGTUUTGAAGTUUTAGUTGGURGTUTUTG AGUTUUAGUUUATGURGAUUUU 539 GTGUARGUAGGGAAATAUUTUAUAGGGTAAATTTGGATURGATTGAGAAUAGGAAG UUAUAGGUUAATAUAAGGAGGUTUTGTGAGAAUAGATGAUAAAUUAUAAGURGGG GAGGGGGAGGAAAGAGUTTTUTGGGUUTGGGGGATGGGXGAGUURGUUAGUAUAU

UAUAUAUAGUTGRGUTTGGUUTUAGTAATUAAAAUUATUATTAUAGAUUTGARGGT TTGGUTGUAGUTGTAAAGAGATAAGUATGTTGGAAGAGAAAAUAGGGUUURGGTG AUURGGUUTTAGGGTUTGAGRGU 540 RGUTUAGAUUUTAAGGURGGGTUAURGGGGUUUTGTTTTUTUTTUUAAUATGUTTA TUTUTTTAUAGUTGUAGUUAAAURGTUAGGTUTGTAATGATGGTTTTGATTAUTGAG GUUAAGRGUAGUTGTGTGTGGTGTGUTGGRGGGUTXGUUUATUUUUUAGGUUUAG AAAGUTUTTTUUTUUUUUTUUURGGUTTGTGGTTTGTUATUTGTTUTUAUAGAGUUT UUTTGTATTGGUUTGTGGUTTUUTGTTUUUAATRGGATUUAAATTTAUUUTGTGAGG TATTTUUUTGRGTGUAUA 541 TGTGRGGGUAGTGGGTTGTGRGGGUAGTGGGTTGTGUATURGGATGTGTAGUAUTU AUAUAUTTRGGGTGAUTUTTUUTGGGTAAGUTGTGGATGTGAGTGGGGGUAGUATU TGURGTGAUTUATTUTUTUUTUTTTUUATTUUAAGUXGGGTGGGGGAGTTTGGGATT TUUAGAUAAGGUUTGGUTUUUUUTGGUAUAGAGGGTGGGAGTGGGGATGGGGAGG GAGGAGGGAAGGGTUATGGGAAGGTGGGGUUATGTTTTGTGUTUAATGAAUTGAGA AGGGGGAGGGTTUUAGUTGG 542 UAGUTGGAAUUUTUUUUUTTUTUAGTTUATTGAGUAUAAAAUATGGUUUUAUUTTU UUATGAUUUTTUUUUUTUUUTUUUUATUUUUAUTUUUAUUUTUTGTGUUAGGGGG AGUUAGGUUTTGTUTGGAAATUUUAAAUTUUUUUAUUXGGUTTGGAATGGAAAGA GGAGAGAATGAGTUARGGUAGATGUTGUUUUUAUTUAUATUUAUAGUTTAUUUAG GAAGAGTUAUURGAAGTGTGTGAGTGUTAUAUATURGGATGUAUAAUUUAUTGUU RGUAUAAUUUAUTGUURGUAUAA 543 GUAAUTGGRGUTGGGTAGGUAAAGURGGGAGAAAUTGUTGAGARGAGGTTAGGAT TTAAUUTTTAAATTUTGGAGUUATRGGAAAURGAGGGGAGGARGARGGGTGTRGGT GUTAATGAGGUTGGGGGRGGGRGATGRGRGGTGGGUUTUXGAGTURGGGGUAGGT UTRGGGGGTTUUURGGGGAAGGUUUTGGGAGUUUTTGGUUUTGGRGGUUTURGUU ATUAGAUTGGGAATGTUTUTGATTGGGTGGUUAGGAGGRGGTGGUUUTUUTUUURG UUUAGUTGAGGGGTGTRGTUTTU 544 GAAGARGAUAUUUUTUAGUTGGGRGGGGAGGAGGGUUAURGUUTUUTGGUUAUUU AATUAGAGAUATTUUUAGTUTGATGGRGGAGGURGUUAGGGUUAAGGGUTUUUAG GGUUTTUUURGGGGAAUUUURGAGAUUTGUUURGGAUTXGGAGGUUUAURGRGUA TRGUURGUUUUUAGUUTUATTAGUAURGAUAUURGTRGTUUTUUUUTRGGTTTURG ATGGUTUUAGAATTTAAAGGTTAAATUUTAAUUTRGTUTUAGUAGTTTUTUURGGUT TTGUUTAUUUAGRGUUAGTTGU 545 GGGUAUUUTUTGGTGUTTUUAGGUUTGTGAATTGGUAUAGUAGGAUUAUAGAUUT UUAAGGTGUUUAUUTGGGGGUTUAGAAUUUTGGRGGGGAAGGTUAGTGUTATUUU AURGGAGAAGAGAUUTAGTUTAGUTGAGUUUUTGGUUAGXGGUAAGGAGGAAAGG ATGAAUATUAGUUARGUUTGGUAUTGAUTGUUAUAGUUAGAGUUTRGUUUAGUUU AAGAATGTTTUTGTTUTAAGAUTTTTTTUTTTTTTGTATTTTAGAGAAGTTUUU AAATGTUAUUTTGAAGAUURGG 546 URGGGTUTTUAAGGTGAUATTTGUUTGTGATAATTTUTAAAATAUAAAAAAGAAAA AAGTUTTAGAAUAGAAAUATTUTTGGGUTGGGRGAGGUTUTGGUTGTGGUAGTUAG TGUUAGGRGTGGUTGATGTTUATUUUTTUUTTTTTTGUXGUTGGUUAGGGGUTUAGU TAGAUTAGGTUTUTTUTURGGTGGGATAGUAUTGAUUTTUUURGUUAGGGTTUTGA GUUUUUAGGTGGGUAUUTTGGAGGTUTGTGGTUUTGUTGTGUUAATTUAUAGGUUT GGAAGUAUUAGAGGGTGUUU 547 UTUATGGAGAGGAGUAGAGATGUAGGAAARGUAAUAGUAGUARGGUAGAAARGUA GGAGAAAUAGUUURGUUTUAGAGURGUUUAUUTUUTUURGUUATGUUAGGAAGGG UUAGTGTUUUTUUAGARGURGGTGAUTGTUARGTUAGAUAXGTGARGTGTGGUTGT GUUUAGATTUTTGGRGGTGAGUUURGGRGAGGGAUUUAGRGGTUTUURGGRGTUTG GTTTAGGGGGGGATUTURGUAAGAUUURGUURGUARGTGGUTUUTGTGAGGGGUAU TGRGRGRGAAGGUTGTGGTUTG 548 UAGAUUAUAGUUTTRGRGRGUAGTGUUUUTUAUAGGAGUUARGTGRGGGRGGGGT UTTGRGGAGATUUUUUUUTAAAUUAGARGURGGGAGAURGUTGGGTUUUTRGURG GGGUTUAURGUUAAGAATUTGGGUAUAGUUAUARGTUAXGTGTUTGARGTGAUAG TUAURGGRGTUTGGAGGGAUAUTGGUUUTTUUTGGUATGGRGGGAGGAGGTGGGRG GUTUTGAGGRGGGGUTGTTTUTUUTGRGTTTUTGURGTGUTGUTGTTGRGTTTU UATUTUTGUTUUTUTUUATGAG 549 UTUTUUAUTGTGUAGGUUAUUTGTAGGGAUAGTGUUAGTGGGTGTAGGAGAGGTGG RGAGGUTGUAGUAGTGRGGGATGGGUTUUUUAUAUUUUUAAATAUTUUAUATGGG GTURGGGGUUTTUUUAGGAUUTGGGUUAGGTGXGUAXGUUTGGGXGGGGUUAGUU AGUTRGTGUTGAGTUAURGGGTGURGTUAGTGAGGGUUTGGUUUUAUUUTRGGGAA UUAURGGTGUTGGTTTTUUUARGGUTGUTGUURGUTGTGGGUUTTGUTGTUAUUUA UAAGGUUUTGGGAGGUUUTGUU 550 GGUAGGGUUTUUUAGGGUUTTGTGGGTGAUAGUAAGGUUUAUAGRGGGUAGUA GURGTGGGAAAAUUAGUAURGGTGGTTUURGAGGGTGGGGUUAGGUUUTUAUTG ARGGUAUURGGTGAUTUAGUARGAGUTGGUTGGUUUXGUUUAGGXGTGXGUAU UTGGUUUAGGTUUTGGGAAGGUUURGGAUUUUATGTGGAGTATTTGGGGGTGTG GGGAGUUUATUURGUAUTGUTGUAGUUTRGUUAUUTUTUUTAUAUUUAUTGGUA UTGTUUUTAUAGGTGGUUTGUAUAGTGGAGAG

[0146] Also provided herein is a deoxyribonucleic acid identical to 5-10, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-110, 110-120, 120-130, 130-140, 140-150, 150-160, 160-170, 170-180, 180-190, or 190-200 of contiguous nucleotide sequence of the sequence including a sequence of SEQ ID NO: 1 to SEQ ID NO: 550.

[0147] In embodiments, provided herein is a deoxyribonucleic acid which includes a methylation site set forth in Table 1.

[0148] In embodiments, included herein is a deoxyribonucleic acid in which a plurality of methylation sites set forth in Table 1 are methylated or unmethylated. In embodiments, the plurality of methylation sites comprises at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, or 550 methylation sites. In embodiments, the plurality of methylation sites comprises between 1-50, 50-100, 100-250, 100-300, 100-400, 100-500, 100-550, 250-550, or 350-500 methylation sites.

Compositions for Detecting Methylation

[0149] Also provided herein are probes and primers that are complementary to one or more of SEQ ID NOS: 1-550. In embodiments, pairs of primers complementary to nucleotide sequences on either side of a methylation site of interest listed in Table 1 are provided. In embodiments, a plurality of probes and/or primers are provided to detect and/or amplify a polynucleotide (e.g., a polynucleotide obtained by bisulfite treatment of DNA) comprising a methylation site of interest. In embodiments, a probe or primer is complementary to a polynucleotide sequence that encompasses the methylation site of interest. In embodiments, the probe or primer is complementary to a sequence that is proximal to the methylation site of interest (e.g., within 1000, 900, 800, 700, 600, 500, 400, 300, 200, 100, 75, 50, or 25 nucleotides of the methylation site of interest in a genomic or bisulfite-treatment-derived polynucleotide).

[0150] In embodiments, a deoxyribonucleic acid selected from SEQ ID NO:551 to SEQ ID NO: 782 is included. In embodiments, the deoxyribonucleic acid selected from SEQ ID NO:551 to SEQ ID NO: 782 is hybridized to a complementary DNA sequence having uridine or cytosine. In embodiments, each of the nucleic acids is different. In embodiments, each of the nucleic acids does not simultaneously have the same sequence selected from SEQ ID NO:551 to SEQ ID NO:782.

[0151] In embodiments, aspects include a deoxyribonucleic acid selected from SEQ ID NO:551 to SEQ ID NO:782, hybridized to corresponding a complementary DNA sequence having uridine or cytosine, and in a complex with an enzyme, e.g., a thermostable DNA polymerase. In embodiments, the thermostable DNA polymerase is Taq DNA polymerase.

[0152] In some aspects, the method includes deoxyribonucleic acid that has a sequence that is at least 50%-55%, 55%-60%, 60%-65%, 65%-70%, 70%-75%, 75%-80%, 80%-85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical or homologous to a nucleic acid having a sequence of at least one of SEQ ID NO:551 to SEQ ID NO:782.

TABLE-US-00006 TABLE 5 SEQ ID NO: Sequence, 5' to 3' 551 GGGAGAAGAGATTGGAAAA 552 CTAAAAACCTAACACTAACAACATAAT 553 TGTTGTTTAAAATGTTGTTT 554 AACCCTAAATAATTCTTCTC 555 GGGTTGGGTTGAGGTTTT 556 ACACCTTACATCTCATTTACAACTC 557 AATTTGTGAAAAGTTTGTGTA 558 CCCAATCACCTTTAATCT 559 GTTGGGATTTGAAATAGTGA 560 CCTCCACTCACCTAAAACTT 561 TTGGTTAGTGATTATTTATT 562 AAAAATTAATATAAAATTAAAA 563 TTTGTAGGGAGTTAGGGAT 564 TCCTCTATCTCACCCTAAAT 565 TTTGATTGAATTATTTGTGTATT 566 ACTCCCTTACTCCTAAACACT 567 AGTGGAGATEGGTAGGGAGA 568 CCCAAAACTAAAACCAAATATAA 569 TTGTGGTTAAATTTATTG 570 ACCCAACAAAATAATATC 571 TGAGGTAGAGTTGTGTGTATAT 572 ATCAATCAATTCTCATTAAAC 573 GGAAGTTAGGAAGGGTTGT 574 CTCCAACTCCAACTAAAACTC 575 TTEGGGTATTGATTTATTTT 576 AAATTCTACCTACAAACTATACA 577 AGGATGAAGTAATAATTAAATATTG 578 CCCACTCTACCAACTAAAC 579 AGGTTTGTGTTAGTATAAAT 580 TTCTTACCTATATAATTAATAATA 581 GTTGGGTGAATTTTATTAG 582 TCAAAACCTAAACTCTAACA 583 GGATTGGTTTRATATAGAAAGTAT 584 CAAATAATAAATCATAACTCTTAACT 585 TGGGGTAGTTGATGGTTT 586 CTTTCTAACAAAATAAAAAAATTTAA 587 TTGTATTTGAAGTTTGTAGAGATTTATA 588 TTTCCTCCAACAACTCAAT 589 TTATGAGTATGTAGTAGGGTTATTATA 590 AAAATATCAAACAAATTTATCC 591 TGGTTGTTTGTTTTTTATGTATT 592 TCCCTACCTCCCAAATTC 593 TATGATGATTGTTGTAGTGTAGA 594 CCTCCCTAATAACTAAAAATAC 595 GGTGGTTTTGATATTTAGTG 596 CCCAATTACCTAACAAATTA 597 TGGGATAGGTGTAGATATG 598 CAACAAAAACTAAAACACTATAC 599 TTTGGGATTGGTTATTTT 600 AAACCCCTTAACTCTATACC 601 GATTTTTTTGAGAAGAGTATAG 602 AACCACTACCACCTAAATATA 603 GGAGGATAGGGTGTGATT 604 ACATTTTTAACTCTAACTAAAAATAAA 605 TGGAAATGAGGTGAGTTT 606 AAAAAAAAATAAAATAACAATAACTA 607 TGGAGAGTTTAGTTTGTTT 608 CAAAAAAAAATCTAACAAC 609 TGGGTTTTAGTTATGTGGTT 610 ATCAATAATATCCAACAAAATAATAT 611 TTTTTTTAGTTTTTGTATATATATTAG 612 ACCCAAATAATCAACTCTT 613 GTGGTTTTTGGAGATTTA 614 AAACAAACTACAAATAAAATAATAC 615 GGGTTATAGGTTTGAGTTA 616 CCATTAAAAAAAATAAAATC 617 TTGGTAGATTTAGTAAATTTATT 618 AAACTTAAACAACCCTATATAC 619 ATGGTTTTAAAGAGTAGTAGTATAGTT 620 AAATTTACTCATCCCACTTC 621 AGGGGTTGGGATATTGTT 622 AAAAATTTCTCCTTACAAAAAACTAA 623 ATGGGTGTTTGGAATTTTTTA 624 CTACCTCAACCTCCTAAATAACTAA 625 GTGTTTTGTGGTANAGATATAG 626 ATTCTTAAATTAATTCAACTACAT 627 TGGGGGTAAAAGTTATAGTT 628 AAAAAACAAAAAACCAAATAC 629 GTTTTTTGGTTAGTGTGTT 630 CCCCATACTTCTATACTATAAT 631 TTGTTGTTTTTAAAGAAATTATA 632 ATCATCTAAACTTAACTCATCTAA 633 ATTTTTGGGTGTTTTATATT 634 AAACCTCAAACAATAACA 635 ATTAAGGATATTTAGGAGAGTAAG 636 ACACCACAACTTCAAACTAC 637 TGAGGAAGAGAGAAGAGATGATA 638 AAAACTAAACTATAAAACAAAACAAAACTA 639 GGTGGAGGTGTTTTTTATAG 640 CCAAATACTACTTTCAAAATACA 641 ATGGATTATTATTGTGTTATT 642 CATCTCAACCTCATACTAA 643 GGATGATTTAGTAGGGATTGAG 644 ccAAATAAAAACCATTCTCTAAC 645 TTGGATTAAGTATTTTTGATATTA 646 TCCCTAAACCATATATTACTAAA 647 GGGTAGTTTGGTGATTATTATT 648 CCCTTCCCTACTCACAATA 649 ATTTGGTTAGTGATTTAGTTATT 650 TCCCACTTAAAAAATTCTATA 651 AGTGGGGAAGGTAATTGTTAT 652 CTTTCTAATAAAAATTTACTAAAACCTCTA 653 TTTGGTTAGTTTTATTTTTGATTG 654 ATTCCTCCCTATCCCTATTC 655 GGGATAGGGGTTAGAGTAA 656 TCCATAAAAACAAAACACTC 657 TTTTTTAGTATGAGTTATAAATTAT 658 AAAACAAAATCTACCTATATATT 659 TTTTATTAATAAAGTAGGTATGA 660 ACCTTTCTCAAAATTACTAA 661 ATAGGGTTGAGGTTAGAGTTAT 662 CCTCCTCTCCACAATAAA 663 TTTAAGTTTTTTTTTAGTTTTGTAGT 664 CCCCATCCTCTCTATCTC 665 AAATTTAAAATTTAGAGGTTTTTATA 666 AAACTTCACACACAAATCTATATT 667 TTTTTATTTTATTTTTTATTTTTAA 668 ATACCTCCCTAATTATATTATTAA 669 TTTTAGAATATTTAAAGAAGTTAGT 670 TAACCTCACTTTCCTATCA 671 AATTTAGTATAAGATTTGATTTGTTA 672 CCACCTACTCCTTCCTATAC 673 TTTTTTGAAATTGTATGTTAT

674 CAAATCCTTAAAATTCTATAA 675 TTTGAAGTGGTGTTTTAG 676 CCAAAATTCTTCCATACT 677 TGGGTATTTAGTYTTTTGTG 678 AACAAcTACCTCCTTTTACTAAT 679 TATGGTAGGAGGTGGAGTT 680 CCCAATTTTAAAACAATAC 681 AGAGGAAGTAAGGTTATTAGTT 682 ACCAAACAAACAATATCTAA 683 GGTTTTAATTATGATTTAATTAGA 684 CCTACACTCAAATTTACCTCTA 685 AATGGGTAGTTGATATAATTATT 686 CACAAAATCCTAAAACTAAAA 687 AGGATTAGTGGAAATGAAAATA 688 TAACCTCAAAACAACTTCTAAAC 689 TTTTTTTTATAGAGAAGTATTTTAG 690 CCCATTACAAAACTATCC 691 GGTGAGTTTGTGGTTAGTG 692 TTTTCTAAAAAAATCCAATCTA 693 AATGGATAGGTTGGAATAG 694 AAAAAAAAAAAAAAACTAATTAC 695 GAGTTATTTAGTTTGGTTAGGT 696 ACTCAACTTAAAAAATCACTATAC 697 TTTYTTTTGGYTTTTTGGYTTT 698 TCCCCCACACCCATATAA 699 TTAAAAAAAAGTATAATGAGTAGGA 700 CCCACAAAAACTCTCTACA 701 AAAGGAGGTTGAGTTAGAAAGTAG 702 AACTATTTAACTTACTTAACCACACC 703 GGTGTGGTTAAGTAAGTTAAATAGT 704 TACCCCTTCCTCTTCAAC 705 TTTTGATATGATTTATGATTATAT 706 TTTTCCACTAAACAACACTA 707 TTTGAGGGTTGTTTTAGAT 708 ACTCACAAAAAATAACTAATAACTAT 709 AAAGGAGGTAGGGGAGATATA 710 TCAAAATAAAAACCAAAATTCTC 711 AGGTTAAGTTGGTAGAGGTAGA 712 CAAACTCTAAACTCAAAATATATTC 713 TTTTTATTTTAGTTTTTTTGAGTAG 714 CCCTACAACACTCCTATCTA 715 TTTGGAGTTAGGTTGATAG 716 CAACAATACTCTCACTTACAC 717 AGAAAGATTTTTAAATATTTTTAAT 718 AAACCTCTAATACACAACAAA 719 TTTTGAGTTTTTTTTTTTTAAGTAT 720 CAAACAAAACAACACTTAATAC 721 GGTTGAGGTGGGTGGATTA 722 TTTTTTTTTTTTTTTTTTAAAATAAAATCT 723 GGGTGTTTGTAATTTTAGTT 724 ACCTETTAACAACCTAACAATATA 725 GGGTAGATGATATGGTAGTGA 726 AAAAAATAAAAAATAACTAAAACAATAT 727 AGGAAGTGTTTAAGAAGTAGAA 728 CCTAAAACTCTAAATACAATCTC 729 TTTTTAATTTTTGTTTGTATT 730 AAACCACAATCTATTTCTAA 731 TTAGAAAAGAATAATTATAGTTG 732 ACCCTAAAAAAATAAAATC 733 TTGTATTAGTAAATAAAGTGTATTTT 734 AACCCTTTCTACAAATCTAC 735 AGGGGTGGGTGGAAGAAT 736 CTCCTCAATAAAATAAAAATCCTAAAAAATA 737 GGGTTAATTAGTTGTTTTAT 738 CCTACAAATATATCACACACT 739 TTTGTTAAATAGGTGGTTAGA 740 ACCTCAACCTCCTAAATAAC 741 TAGGGTTTAGAGTAGGAGGTAG 742 CAAAAAATATAAATCAAAAACATC 743 GGGATTATAGGTATTTATTAT 744 TAAAAATTAAAAATCATACTTA 745 AAGTGATTTTTAGGGAGTGT 746 TCCATAATAACCTCATTTTAATA 747 TTTTTGGTTGAGGTTTAGT 748 AAACAACACAACTCTTATCAC 749 TATGGTGATTAAAGTATAATAGTT 750 TCCTAAATAAAAAACAACATA 751 TGAAAATGTTTTTAGTTTTTATT 752 AAATACCCTACCTCTTATCTAA 753 GATGGTTAATTTTTTTATTT 754 ACTCCTTCAACAAACTAAC 755 AGGGGATATTTTTAGGTT 756 CCAATCTATTCCTATATAATTAA 757 AGGAGAGTTTGGAAATATAG 758 CAATTCTAAATTAAACCTTATT 759 AATAATGGTAGTAGTTTTATTAG 760 TTCCTATATTAACAACTTACA 761 TTTTTTGGTAGATTTTTAT 762 AAATTAATTTCTATTATTTATATTA 763 AGGTGGTTGGGGAGAGTG 764 CCCTAAAATAAATCAAAAAAAACCTTAA 765 AGGTTTAGGTGGGGTGAAT 766 TAAAATCATCAAAATCCCTTAAAA 767 TTTTTTTTTAGGTTATACTGAGTATT 768 ATCCCCACAAAACACATA 769 TAGGGTAAATATTGGGATTATT 770 TTTCCACCTCAAAACTTAAC 771 GGGTGTTTGTATTTTTATATT 772 ACCTCCCAAAACCATAAC 773 GATGTGAGTGGTGAGGTGGT 774 CAAACCCTTCCAAAACATAAAC 775 TGGGATTATAGGTATGTATT 776 CAATTTCATTTATAAATATAAATAT 777 AGGGGTTGGTTATTTTTATTTT 778 TTTTTAATATTTAATTTTTACCTTCAACT 779 GGTAAGTTGTGGATGTGAGT 780 AAAAAAAACCAAACCTTATCTA 781 TTTTTAGGATTTGGGTTAG 782 AACCTTATAAATAACAACAAAAC

Kit for Detecting Methylation Level of a Thyroid Nodule

[0153] Also provided is a kit including a plurality (e.g., at least about 10, 20, 40, 50, 100, 150, 200, 225, or 232) nucleic acids each independently comprising one sequence selected from SEQ ID NO:551 to SEQ ID NO:782, in which the nucleic acids do not simultaneously include the same sequence.

[0154] In some aspects, the kit includes deoxyribonucleic acid that has a sequence that is at least 50%-55%, 55%-60%, 60%-65%, 65%-70%, 70%-75%, 75%-80%, 80%-85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical or homologous to a nucleic acid having a sequence of at least one of SEQ ID NO:551 to SEQ ID NO:782.

[0155] The kit provided herein may include enzymes, reagents for deamination of cytosine, buffers, vials, plasmid vectors, control DNA, devices for collecting thyroid tissue samples, reagents for isolating DNA, reagents for labeling DNA, labels, or any combinations thereof.

[0156] The kit provided herein may include enzymes such as thermostable DNA polymerase enzymes, restriction enzymes, and combination thereof.

[0157] In embodiments, the kit(s) may further include enzymes, reagents for deamination of cytosine, buffers, vials, control DNA, devices for collecting blood and/or tissue samples, or reagents for labeling DNA, or any combinations thereof.

[0158] In embodiments, a kit provided herein may include a solid carrier capable of adsorbing the nucleic acids containing in a sample of a body fluid, for example blood (whole blood, plasma, or serum). The kit may also contain other components for example, reagents, in concentrated or final dilution form, chromatographic materials for the separation of the nucleic acids, aqueous solutions (buffers, optionally also in concentrated form for final adjusting by the user) or chromatographic materials for desalting nucleic acids which have been eluted with sodium chloride.

[0159] In embodiments, a kit provided herein includes materials for purifying nucleic acids, for example, inorganic and/or organic carriers and optionally solutions, excipients and/or accessories. Such agents are known and are commercially available. For solid phase nucleic acid isolation methods, many solid supports have been used including membrane filters, magnetic beads, metal oxides, and latex particles.

[0160] In addition, a kit can also contain excipients such as, for example, a protease such as proteinase K, or enzymes and other agents for manipulating nucleic acids. e.g., at least one amplification primer, nucleic acid bases (A, T, G. C, and/or U), and enzymes suitable for amplifying nucleic acids, e.g., DNase, a nucleic acid polymerase and/or at least one restriction endonuclease. Alternatively, a commercial polymerase chain reaction kit may be used to amplify the DNA samples.

Exemplary Techniques for Detecting Specific Sequences

[0161] Specific sequences, such as the sequences listed in Table 1 (or portions thereof containing a methylation site of interest), can be detected by numerous methods that are well-established in the art (e.g., PCR-based sequence specific amplification, isozyme markers, northern analysis, sequence specific hybridization, and array based hybridization). In embodiments, the presence or absence of methylation is determined through nucleotide sequencing of the site of interest (e.g., the site in bisulfite-treated DNA or an amplicon thereof). Any of these methods are readily adapted to high throughput analysis.

[0162] Some techniques for detecting specific sequences utilize hybridization of a probe nucleic acid to nucleic acids corresponding to the methylation site of interest (e.g., amplified nucleic acids produced using bisulfite-treated DNA as a template or the bisulfite-treated DNA itself). Hybridization formats, including, but not limited to: solution phase, solid phase, mixed phase, or in situ hybridization assays are useful for sequence detection. A non-limiting guide to the hybridization of nucleic acids is found in Tijssen (1993) Laboratory Techniques in Biochemistry and Molecular Biology--Hybridization with Nucleic Acid Probes Elsevier, N.Y., as well as in Sambrook. Berger and Ausubel.

[0163] Nucleic acid probes complementary to a methylation site can be cloned and/or synthesized. Any suitable label can be used with a probe. Detectable labels suitable for use with nucleic acid probes include, for example, any composition detectable by spectroscopic, radioisotopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. Useful labels include biotin for staining with labeled streptavidin conjugate, magnetic beads, fluorescent dyes, radiolabels, enzymes, and colorimetric labels. Other labels include ligands which bind to antibodies labeled with fluorophores, chemiluminescent agents, and enzymes. A probe can also constitute radiolabelled PCR primers that are used to generate a radiolabelled amplicon. Labeling strategies for labeling nucleic acids and corresponding detection strategies can be found, e.g., in Haugland (2003) Handbook of Probes and Research Chemicals Ninth Edition by Molecular Probes, Inc. (Eugene Oreg.). Additional non-limiting details regarding sequence detection strategies are found below.

[0164] PCR, RT-PCR and LCR are in particularly broad use as amplification and amplification-detection methods for amplifying nucleic acids (e.g., those comprising a methylation site), facilitating detection of the nucleic acids of interest.

[0165] In embodiments, real time PCR or LCR is performed on the amplification mixtures described herein. e.g., using molecular beacons or TaqMan.TM. probes. A molecular beacon (MB) is an oligonucleotide or peptide nucleic acid (PNA) which, under appropriate hybridization conditions, self-hybridizes to form a stem and loop structure. The MB has a label and a quencher at the termini of the oligonucleotide or PNA; thus, under conditions that permit intra-molecular hybridization, the label is typically quenched (or at least altered in its fluorescence) by the quencher. Under conditions where the MB does not display intra-molecular hybridization (e.g., when bound to a target nucleic acid, e.g., to a region of an amplicon during amplification), the MB label is unquenched. Details regarding standard methods of making and using MBs are well established in the literature and MBs are available from a number of commercial reagent sources. See also, e.g., Leone et al. (1995) "Molecular beacon probes combined with amplification by NASBA enable homogenous real-time detection of RNA." Nucleic Acids Res. 26:2150-2155; Tyagi and Kramer (1996) "Molecular beacons: probes that fluoresce upon hybridization" Nature Biotechnology 14:303-308; Blok and Kramer (1997) "Amplifiable hybridization probes containing a molecular switch" Mol Cell Probes 11:187-194; Hsuih et al. (1997) "Novel, ligation-dependent PCR assay for detection of hepatitis C in serum" J Clin Microbiol 34:501-507; Kostrikis et al. (1998) "Molecular beacons: spectral genotyping of human alleles" Science 279:1228-1229; Sokol et al. (1998) "Real time detection of DNA:RNA hybridization in living cells" Proc. Natl. Acad. Sci. U.S.A. 95:11538-11543; Tyagi et al. (1998) "Multicolor molecular beacons for allele discrimination" Nature Biotechnology 16:49-53; Bonnet et al. (1999) "Thermodynamic basis of the chemical specificity of structured DNA probes" Proc. Natl. Acad. Sci. U.S.A. 96:6171-6176; Fang et al. (1999) "Designing a novel molecular beacon for surface-immobilized DNA hybridization studies" J. Am. Chem. Soc. 121:2921-2922; Marras et al. (1999) "Multiplex detection of single-nucleotide variation using molecular beacons" Genet. Anal. Biomol. Eng. 14:151-156; and Vet et al. (1999) "Multiplex detection of four pathogenic retroviruses using molecular beacons" Proc. Natl. Acad. Sci. U.S.A. 96:6394-6399. Additional details regarding MB construction and use is found in the patent literature, e.g., U.S. Pat. No. 5,925,517 (Jul. 20, 1999) to Tyagi et al. entitled "Detectably labeled dual conformation oligonucleotide probes, assays and kits;" U.S. Pat. No. 6,150,097 to Tyagi et al (Nov. 21, 2000) entitled "Nucleic acid detection probes having non-FRET fluorescence quenching and kits and assays including such probes" and U.S. Pat. No. 6,037,130 to Tyagi et al (Mar. 14, 2000), entitled "Wavelength-shifting probes and primers and their use in assays and kits."

[0166] PCR detection and quantification using dual-labeled fluorogenic oligonucleotide probes, commonly referred to as "TaqMan.TM." probes, can also be performed. These probes are composed of short (e.g., 20-25 base) oligodeoxynucleotides that are labeled with two different fluorescent dyes. On the 5' terminus of each probe is a reporter dye, and on the 3' terminus of each probe a quenching dye is found. The oligonucleotide probe sequence is complementary to an internal target sequence present in a PCR amplicon. When the probe is intact, energy transfer occurs between the two fluorophores and emission from the reporter is quenched by the quencher by FRET. During the extension phase of PCR, the probe is cleaved by 5' nuclease activity of the polymerase used in the reaction, thereby releasing the reporter from the oligonucleotide-quencher and producing an increase in reporter emission intensity. Accordingly, TaqMan.TM. probes are oligonucleotides that have a label and a quencher, where the label is released during amplification by the exonuclease action of the polymerase used in amplification. This provides a real time measure of amplification during synthesis. A variety of TaqMan.TM. reagents are commercially available, e.g., from Applied Biosystems (Division Headquarters in Foster City, Calif.) as well as from a variety of specialty vendors such as Biosearch Technologies (e.g., black hole quencher probes). Further details regarding dual-label probe strategies can be found, e.g., in WO92/02638.

[0167] Other similar methods include e.g. fluorescence resonance energy transfer between two adjacently hybridized probes. e.g., using the "LightCycler.TM." format described in U.S. Pat. No. 6,174,670.

Amplification and Sequencing Primers

[0168] In embodiments, methylation sites are detected using primers, e.g., to amplify and/or sequence polynucleotides comprising the methylation sites.

[0169] Suitable primers can be designed and is not intended that the present subject matter be limited to any particular primer or primer pair. For example, primers can be designed using any suitable software program, such as LASERGENE.TM., e.g., taking account of publicly available sequence information. Flanking sequences for the methylation sites identified herein are publicly available; accordingly, suitable amplification primers can be constructed based on well understood base-pairing rules. The sequence of any amplicon can be detected as has already been discussed above. e.g., by sequencing, hybridization, array hybridization, PCR, LCR, or the like.

[0170] In embodiments, the primers are radiolabelled, or labeled by any suitable means (e.g., using a non-radioactive fluorescent tag), to allow for rapid visualization of differently sized amplicons following an amplification reaction without any additional labeling step or visualization step. In embodiments, the primers are not labeled, and the amplicons are visualized following their size resolution, e.g., following agarose or acrylamide gel electrophoresis. In embodiments, ethidium bromide staining of the PCR amplicons following size resolution allows visualization of the different size amplicons.

[0171] It is not intended that the primers be limited to generating an amplicon of any particular size. The primers can generate an amplicon of any suitable length for detection (e.g., by sequencing or hybridization). In embodiments, amplification produces an amplicon at least 20 nucleotides in length, or alternatively, at least 50 nucleotides in length, or alternatively, at least 100 nucleotides in length, or alternatively, at least 200 nucleotides in length. Amplicons of any size can be detected and/or sequenced using various technologies described herein and known in the art.

Detection of Methylation Levels Using Sequencing

[0172] Sequencing is the process of determining the precise order of nucleotides within a DNA molecule. The advent of rapid DNA sequencing methods has greatly accelerated biological and medical research and discovery. Non-limiting examples and descriptions are provided below. However, embodiments are not limited to the use of a particular sequencing assay, technology, or approach.

[0173] Sanger sequencing is a method of DNA sequencing based on the selective incorporation of chain-terminating dideoxynucleotides by DNA polymerase during in vitro DNA replication (Sanger F; Coulson A R (May 1975) J. Mol. Biol. 94 (3): 441-8; Sanger et al. (December 1977) Proc. Natl. Acad. Sci. U.S.A. 74 (12): 5463-7).

[0174] In embodiments, next-generation sequencing is used. Non-limiting examples of next-generation sequencing methods include massively parallel signature sequencing (MPSS), single-molecule real-time sequencing, ion semiconductor sequencing, pyrosequencing, sequencing by synthesis, sequencing by ligation, chain termination. DNA nanoball sequencing, helicos single molecule sequencing, single molecule real time sequencing, nanopore DNA sequencing, tunnelling currents DNA sequencing, and sequencing by hybridization.

[0175] Many commercially available sequencing technologies, devices, and services are available. In embodiments, an Illumina sequencer is used. In embodiments, PCR products are ligated with a linker and sequenced using a high throughput sequencer, such as an Illumina sequencer. In embodiments, the ligation step can be avoided, omitted, or eliminated by adding a linker to amplification primers.

Array-Based Sequence Detection

[0176] Array-based detection can be performed using commercially available arrays, e.g., from Affymetrix (Santa Clara, Calif.) or other manufacturers. Reviews regarding the operation of nucleic acid arrays include Sapolsky et al. (1999) "High-throughput polymorphism screening and genotyping with high-density oligonucleotide arrays." Genetic Analysis: Biomolecular Engineering 14:187-192; Lockhart (1998) "Mutant yeast on drugs" Nature Medicine 4:1235-1236; Fodor (1997) "Genes. Chips and the Human Genome." FASEB Journal 11:A879; Fodor (1997) "Massively Parallel Genomics." Science 277: 393-395; and Chee et al. (1996) "Accessing Genetic Information with High-Density DNA Arrays." Science 274:610-614.

[0177] A variety of probe arrays have been described in the literature and can be used for detection of methylation. For example, DNA probe array chips or larger DNA probe array wafers (from which individual chips would otherwise be obtained by breaking up the wafer) may be used in embodiments described herein. DNA probe array wafers generally comprise glass wafers on which high density arrays of DNA probes (short segments of DNA) have been placed. Each of these wafers can hold, for example, approximately 60 million DNA probes that are used to recognize longer sample DNA sequences (e.g., from individuals or populations, e.g., that comprise methylation sites of interest). The recognition of sample DNA by the set of DNA probes on the glass wafer takes place through DNA hybridization. When a DNA sample hybridizes with an array of DNA probes, the sample binds to those probes that are complementary to the sample DNA sequence. By evaluating to which probes the sample DNA for an individual hybridizes more strongly, it is possible to determine whether a known sequence of nucleic acid is present or not in the sample, thereby determining whether a uracil, thymine, or cytosine is present at a polynucleotide site corresponding to a genomic methylation site. One can also use this approach to control the hybridization conditions to permit single nucleotide discrimination, e.g., for the identification of methylation at a site of interest. Arrays provide one convenient embodiment for detecting multiple methylation sites simultaneously (or in series). Of course, any detection technology (PCR, LCR, and/or sequencing etc.) can similarly be used, e.g., with multiplex amplification/detection/sequencing reactions, or simply by running several separate reactions. e.g., simultaneously or in series.

[0178] In embodiments, the use of DNA probe arrays to obtain methylation information involves the following general steps: design and manufacture of DNA probe arrays, preparation of the sample, bisulfite treatment, hybridization of sample DNA to the array, detection of hybridization events and data analysis to determine sequence. In embodiments, an array is used to capture polynucleotides containing a methylation site of interest, and the captured polynucleotides are subsequently amplified and/or sequenced. Preferred wafers are manufactured using a process adapted from semiconductor manufacturing to achieve cost effectiveness and high quality, and are available, e.g., from Affymetrix, Inc. of Santa Clara, Calif.

[0179] For example, probe arrays can be manufactured by light-directed chemical synthesis processes, which combine solid-phase chemical synthesis with photolithographic fabrication techniques as employed in the semiconductor industry. Using a series of photolithographic masks to define chip exposure sites, followed by specific chemical synthesis steps, the process constructs high-density arrays of oligonucleotides, with each probe in a predefined position in the array. Multiple probe arrays can be synthesized simultaneously on a large glass wafer. This parallel process enhances reproducibility and helps achieve economies of scale.

[0180] In embodiments, DNA probe arrays can be used to obtain data regarding presence of sequences (e.g., corresponding to methylated or unmethylated DNA) of interest. The DNA samples may be tagged with biotin and/or a fluorescent reporter group by standard biochemical methods. The labeled samples are incubated with an array, and segments of the samples bind, or hybridize, with complementary sequences on the array. The array can be washed and/or stained to produce a hybridization pattern. The array is then scanned and the patterns of hybridization are detected by emission of light from the fluorescent reporter groups. Because the identity and position of each probe on the array is known, the nature of the DNA sequences in the sample applied to the array can be determined.

[0181] In embodiments, the nucleic acid sample to be analyzed is isolated, bisulfite-treated, amplified and, optionally, labeled with biotin and/or a fluorescent reporter group. The labeled nucleic acid sample may then incubated with the array using a fluidics station and hybridization oven. The array can be washed and or stained or counter-stained, as appropriate to the detection method. After hybridization, washing and staining, the array is inserted into a scanner, where patterns of hybridization are detected. The hybridization data are collected as light emitted from the fluorescent reporter groups already incorporated into the labeled nucleic acid, which is now bound to the probe array. Probes that most clearly match the labeled nucleic acid produce stronger signals than those that have mismatches. Since the sequence and position of each probe on the array are known, by complementarity, the identity of the nucleic acid sample applied to the probe array can be identified. In embodiments, hybridization techniques and conditions that allow only fully complementary nucleotide sequences to hybridize with probes in an array are used.

[0182] Prior to amplification and/or detection of a nucleic acid comprising a sequence of interest, the nucleic acid is optionally purified from the samples by any available method, e.g., those taught in Berger and Kimmel, Guide to Molecular Cloning Techniques, Methods in Enzymology volume 152 Academic Press. Inc., San Diego. Calif. (Berger); Sambrook et al., Molecular Cloning--A Laboratory Manual (3rd Ed.), Vol. 1-3. Cold Spring Harbor Laboratory, Cold Spring Harbor. N.Y., 2001 ("Sambrook"); and/or Current Protocols in Molecular Biology. F. M. Ausubel et al., eds., Current Protocols, a joint venture between Greene Publishing Associates. Inc, and John Wiley & Sons, Inc., (supplemented through 2002) ("Ausubel")). A plethora of kits are also commercially available for the purification of nucleic acids from cells or other samples (see. e.g., EasyPrep.TM., FlexiPrep.TM., both from Pharmacia Biotech; StrataClean.TM., from Stratagene; and, QIAprep.TM. from Qiagen). Alternately, samples can simply be directly subjected to amplification or detection, e.g., following aliquotting and/or dilution.

Thyroid Cancer Diagnostic System and Processes

[0183] FIG. 4 depicts a block diagram illustrating an exemplary thyroid cancer diagnostic system 600. Referring to FIG. 4, the thyroid cancer diagnostic system 600 can include an input module 610, an isolation module 612, a conversion module 614, a detection module 616, a diagnosis module 618, a treatment module 620, and a user interface (UI) module 622. The thyroid cancer diagnostic system 600 can be configured to provide a diagnosis indicative of a presence of thyroid cancer and/or a risk of developing thyroid cancer. Moreover, the thyroid cancer diagnostic system 600 can be further configured to generate a treatment plan for a subject based on the diagnosis. For instance, when the diagnosis indicates a presence and/or risk of thyroid cancer in a subject, the thyroid cancer diagnostic system 600 can recommend one or more treatments including, for example, thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and administration of an active agent.

[0184] One or more modules of the thyroid cancer diagnostic system 600 can be realized in digital electronic circuitry, integrated circuitry, specially designed application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs) computer hardware, firmware, software, and/or combinations thereof. The thyroid cancer diagnostic system 600 can further be communicatively coupled with one or more devices including, for example, a device 630. The thyroid cancer diagnostic system 600 can communicate with the device 620 via a wired and/or wireless network 640 (e.g., a wide area network (WAN), a local area network (LAN), and/or the Internet). As shown in FIG. 4, the thyroid cancer diagnostic system 600 can be further coupled with a data store 650.

[0185] The input module 610 can be adapted to receive and/or collect a sample of a thyroid nodule obtained from a subject. The isolation module 612 can be configured to isolate DNA from the thyroid nodule sample received by the input module 610 thereby forming isolated thyroid nodule DNA. The conversion module 614 can be configured to treat the isolated thyroid nodule DNA including by contacting the isolated thyroid nodule DNA with one or more bisulfite reagents including, for example, a bisulfite salt. Exposing the isolated thyroid nodule DNA to one or more bisulfite reagents can convert cytosine to uracil while 5-mC is left unmodified. Thus, the 5-mC present in the isolated thyroid nodule DNA will remain in the reacted thyroid nodule DNA. Meanwhile, any cytosine in the isolated thyroid nodule DNA will be replaced by uracil in the reacted thyroid nodule DNA. In embodiments, the treatment of the isolated thyroid nodule DNA can be performed by applying one or more kits (e.g., the Bisulflash DNA Modification Kit (Epigentek) or Imprint DNA Modification Kit (Sigma)).

[0186] In embodiments, the conversion module 614 can be further adapted to ensure optimal bisulfite conversion (e.g., with desired DNA fragment size for post-bisulfite ligation) by controlling one or more of a concentration of the bisulfite reagents, temperature, and reaction time period. It should be appreciated that the conversion module 614 can be adapted to use a different and/or additional type of reagent without departing from the scope of the present subject matter. For example, the conversion module 614 can treat the isolated thyroid nodule DNA with potassium chloride, which may reduce the thermophilic DNA degradation associated with the conversion of cytosine to uracil. Moreover, the conversion module 614 can be configured to perform additional processing of the reacted thyroid nodule DNA including, for example, desulphonation (e.g., with an alkalized solution), cleansing (e.g., by elution), and amplification (e.g., using the PCR method).

[0187] The detection module 616 can be configured to detect a methylation and/or unmethylation of the thyroid nodule DNA. For instance, the detection module 616 can detect methylation by detecting a presence of uracil in the reacted thyroid nodule DNA generated by the conversion module 614. Alternately and/or additionally, the detection module 616 can detect unmethylation by detecting an absence of uracil in the reacted thyroid nodule DNA. In embodiments, the detection module 616 can be configured detect the presence and/or absence of uracil at specific methylation sites. That is, the detection module 616 can be configured to detect the presence and/or absence of uracil at specific chromosomal positions of certain chromosomes. For example, the thyroid cancer diagnostic system 600 can store a plurality of specific methylation sites (e.g., Table 1) in the data store 650. As such, to detect methylation, the detection module 616 can be configured to obtain, from the data store 650, one or more specific methylation sites at which to test for the presence and/or absence of uracil. Moreover, in embodiments, the detection module 616 can be configured to determine a level of methylation and/or unmethylation at the specific methylation sites. The level of methylation at a particular site can correspond to a proportion of the reacted thyroid nodule DNA that has a cytosine rather than a uracil at that site. By contrast, the level of unmethylation at a particular site can correspond to a proportion of reacted thyroid nodule DNA that has a uracil rather than a cytosine at that site.

[0188] In embodiments, the conversion module 614 may amplify the reacted thyroid nodule DNA such as by using a PCR method. The detection of methylation and/or unmethylation in amplified reacted thyroid nodule DNA may require detection of a presence and/or absence of thymidine at a site of interest in amplicons amplified from the reacted thyroid nodule DNA. That is, instead of detecting the presence and/or absence of uracil, the detection module 616 can be configured to detect methylation and/or unmethylation of amplified reacted thyroid nodule DNA by detecting a presence and/or absence of thymidine at specific methylation sites (e.g., as set forth in Table 1).

[0189] The diagnosis module 618 can be configured to generate a diagnosis for the subject based on whether the detection module 616 detects methylation and/or unmethylation at the plurality of specific methylation sites (e.g., Table 1). Alternately or additionally, the diagnosis module 618 can be configured to generate a diagnosis for the subject based on a level of methylation and/or unmethylation detected by the detection module 616 at the plurality of specific methylation sites. For instance, diagnosis module 618 can determine that the thyroid nodule is malignant (e.g., cancerous) when the unmethylation level (e.g., proportion of uracil) at different methylation sites exceeds the corresponding thresholds (e.g., as set forth in Table 2). In embodiments, the diagnosis module 618 can further generate a diagnosis for the subject based on one or more of the subject's PTC methylation alternation score, a BTN methylation alternation score, and/or a Composite Cancer Risk Score.

[0190] In embodiments, the diagnosis module 618 can be configured to determine a PTC methylation alternation score for the subject. In embodiments, the PTC methylation alteration score can correspond to a number of specific methylation sites (e.g., as set forth in Table 1) that have a uracil level (or corresponding thymidine level if amplicons are being analyzed) equal to or greater than the corresponding thresholds (e.g., as set forth in Table 2). Alternately or additionally, the diagnosis module 618 can be configured to determine a BTN methylation alternation score for the subject. The BTN methylation alteration score can correspond to a number of specific methylation sites (e.g., as set forth in Table 1) that have a uracil level (or corresponding thymidine level if amplicons are being analyzed) equal to or greater than the various corresponding threshold level (e.g., as set forth in Table 3 and/or Table 4).

[0191] In embodiments, the diagnosis module 618 can further be configured to compute a Composite Cancer Risk Score for the subject. The diagnosis module 618 can compute the Composite Cancer Risk Score based on the PTC methylation alteration score and the BTN methylation alteration score for the subject. For example, the Composite Cancer Risk Score for the subject can be computed based on equation (1):

[ the PTC methylation alteration score for the subject ] [ BTN methylation a l teration score for the subject ] . ( 1 ) ##EQU00001##

[0192] Alternately or additionally, the Composite Cancer Risk Score for the subject can be computed based on equation (2):

[ ( the PTC methylation alteration score for the subject ) + 1 ] [ ( BTN methylation alteration score for the subject ) + 1 ] ( 2 ) ##EQU00002##

[0193] The treatment module 620 can be configured to formulate a treatment plan for the subject based on the diagnosis generated by the diagnosis module 618. For instance, when the diagnosis generated by the diagnosis module 618 indicates a presence and/or risk of a malignant (e.g., cancerous) thyroid nodule, the treatment module 620 can prescribe one or more treatments including, for example, thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and administration of an active agent. In embodiments, the treatment module 620 can be configured to provide the treatment plan to the device 630 via the network 640. Alternately or additionally, the treatment module 620 can store the treatment plan in the data store 650.

[0194] The UI module 622 can be configured to generate a UI through which a user (e.g., a physician) can interface with the thyroid cancer diagnostic system 600. For example, the UI module 622 can provide one or more graphic user interfaces (GUIs) configured to display the diagnosis and/or treatment plan for the subject.

[0195] FIG. 5 depicts a flowchart illustrating an exemplary process 700 for diagnosing thyroid cancer. Referring to FIGS. 4-5, the process 700 can be performed by the thyroid cancer diagnostic system 600.

[0196] The thyroid cancer diagnostic system 600 (e.g., the input module 610) can receive a sample of a thyroid nodule from a subject (702). The thyroid cancer diagnostic system 600 (e.g., the isolation module 612) can isolate thyroid nodule DNA from the thyroid nodule sample (704). The thyroid cancer diagnostic system 600 (e.g., the conversion module 614) can treat the isolated thyroid nodule DNA with a bisulfite salt to generate reacted thyroid nodule DNA (706). Treating the isolated thyroid nodule DNA with the bisulfite salt can form a reacted thyroid nodule DNA by converting the cytosine present in the isolated thyroid nodule DNA to uracil. In embodiments, the thyroid cancer diagnostic system 600 can further process the reacted thyroid nodule DNA by desulphonating, cleansing, and/or amplifying the reacted thyroid nodule DNA.

[0197] The thyroid cancer diagnostic system 600 (e.g., the detection module 616) can detect methylation and/or unmethylation of the isolated thyroid nodule DNA by at least detecting a presence and/or absence of uracil in the reacted thyroid nodule DNA (708). In embodiments, the thyroid cancer diagnostic system 600 can be configured to detect a presence and/or absence of uracil at specific methylation sites (e.g., as set forth in Table 1). Moreover, the thyroid cancer diagnostic system 600 can be configured to detect a level of methylation and/or unmethylation at the methylation sites.

[0198] The thyroid cancer diagnostic system 600 (e.g., the diagnostics module 618) can generate a diagnosis for the subject based on the methylation and/or unmethylation of the isolated thyroid nodule DNA (710). For example, the thyroid cancer diagnostic system 600 can generate a diagnosis based on a level of methylation and/or unmethylation at a plurality of specific methylation sites. Each methylation site may be associated with a certain threshold unmethylation level (e.g., as set forth in Table 2). As such, the thyroid cancer diagnostic system 600 can determine that the thyroid nodule from the subject is malignant (e.g., cancerous) if the level of unmethylation at the plurality of methylation sites exceeds the corresponding thresholds.

[0199] The thyroid cancer diagnostic system 600 (e.g., the treatment module 620) can formulate, based on the diagnosis, a treatment plan for the subject (712). For example, when the diagnosis indicates that a presence and/or risk of malignant thyroid nodules in the subject, the thyroid cancer diagnostic system 600 can prescribe thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and/or administration of an active agent. The thyroid cancer diagnostic system 600 (e.g., the UI module 622) can provide, via a UI (e.g., GUI at the device 630), the diagnosis and/or the treatment plan for the subject (714).

[0200] FIG. 6 depicts a flowchart illustrating an exemplary process 800 for diagnosing thyroid cancer. Referring to FIGS. 4 and 6, the process 700 can be performed by the thyroid cancer diagnostic system 600.

[0201] The thyroid cancer diagnostic system 600 (e.g., the input module 610) can receive a sample of a thyroid nodule from a subject (802). The thyroid cancer diagnostic system 600 (e.g., the isolation module 612) can isolate thyroid nodule DNA from the thyroid nodule sample (804). The thyroid cancer diagnostic system 600 (e.g., the conversion module 614) can treat the isolated thyroid nodule DNA with a bisulfite salt to generate reacted thyroid nodule DNA (806).

[0202] As shown in FIG. 6, the thyroid cancer diagnostic system 600 (e.g., the conversion module 614) can amplify the reacted thyroid nodule DNA (808). For instance, the thyroid cancer diagnostic system 600 can amplify the reacted thyroid nodule DNA subsequent to treating the isolated thyroid nodule NA with the bisulfite salt to generate the reacted thyroid nodule DNA. The thyroid cancer diagnostic system 600 can detect methylation and/or unmethylation of the isolated thyroid nodule DNA by detecting a presence and/or absence of thymidine in the amplified reacted thyroid nodule DNA (810).

[0203] The thyroid cancer diagnostic system 600 (e.g., the diagnostics module 618) can generate a diagnosis for the subject based on the methylation and/or unmethylation of the isolated thyroid nodule DNA (812). Moreover, the thyroid cancer diagnostic system 600 (e.g., the treatment module 620) can formulate, based on the diagnosis, a treatment plan for the subject (814). The thyroid cancer diagnostic system 600 (e.g., the UI module 622) can provide, via a UI, the diagnosis and/or treatment plan for the subject.

[0204] It should be appreciated that the process 700 and/or 800 can include different and/or additional operations without departing from the scope of the present subject matter. Moreover, one or more operations of the process 700 and/or 800 can be omitted and/or repeated without departing from the scope of the present subject matter.

[0205] Implementations of the present subject matter can include, but are not limited to, methods consistent with the descriptions provided above as well as articles that comprise a tangibly embodied machine-readable medium operable to cause one or more machines (e.g., computers, etc.) to result in operations implementing one or more of the described features. Similarly, computer systems are also described that can include one or more processors and one or more memories coupled to the one or more processors. A memory, which can include a computer-readable storage medium, can include, encode, store, or the like one or more programs that cause one or more processors to perform one or more of the operations described herein. Computer implemented methods consistent with one or more implementations of the current subject matter can be implemented by one or more data processors residing in a single computing system or multiple computing systems. Such multiple computing systems can be connected and can exchange data and/or commands or other instructions or the like via one or more connections, including but not limited to a connection over a network (e.g. the Internet, a wireless wide area network, a local area network, a wide area network, a wired network, or the like), via a direct connection between one or more of the multiple computing systems, etc.

[0206] One or more aspects or features of the subject matter described herein can be realized in digital electronic circuitry, integrated circuitry, specially designed ASICs, FPGAs, computer hardware, firmware, software, and/or combinations thereof. These various aspects or features can include implementation in one or more computer programs that are executable and/or interpretable on a programmable system including at least one programmable processor, which can be special or general purpose, coupled to receive data and instructions from, and to transmit data and instructions to, a storage system, at least one input device, and at least one output device. The programmable system or computing system can include clients and servers. A client and server are generally remote from each other and typically interact through a communication network. The relationship of client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship to each other.

[0207] These computer programs, which can also be referred to programs, software, software applications, applications, components, or code, include machine instructions for a programmable processor, and can be implemented in a high-level procedural language, an object-oriented programming language, a functional programming language, a logical programming language, and/or in assembly/machine language. As used herein, the term "machine-readable medium" refers to any computer program product, apparatus and/or device, such as for example magnetic discs, optical disks, memory, and Programmable Logic Devices (PLDs), used to provide machine instructions and/or data to a programmable processor, including a machine-readable medium that receives machine instructions as a machine-readable signal. The term "machine-readable signal" refers to any signal used to provide machine instructions and/or data to a programmable processor. The machine-readable medium can store such machine instructions non-transitorily, such as for example as would a non-transient solid-state memory or a magnetic hard drive or any equivalent storage medium. The machine-readable medium can alternatively or additionally store such machine instructions in a transient manner, such as for example as would a processor cache or other random access memory associated with one or more physical processor cores.

[0208] To provide for interaction with a user, one or more aspects or features of the subject matter described herein can be implemented on a computer having a display device, such as for example a cathode ray tube (CRT) or a liquid crystal display (LCD) or a light emitting diode (LED) monitor for displaying information to the user and a keyboard and a pointing device, such as for example a mouse or a trackball, by which the user may provide input to the computer. Other kinds of devices can be used to provide for interaction with a user as well. For example, feedback provided to the user can be any form of sensory feedback, such as for example visual feedback, auditory feedback, or tactile feedback; and input from the user can be received in any form, including, but not limited to, acoustic, speech, or tactile input. Other possible input devices include, but are not limited to, touch screens or other touch-sensitive devices such as single or multi-point resistive or capacitive trackpads, voice recognition hardware and software, optical scanners, optical pointers, digital MRI image capture devices and associated interpretation software, and the like.

[0209] Examples are provided below to facilitate a more complete understanding of the invention. The following examples illustrate the exemplary modes of making and practicing the invention. However, the scope of the invention is not limited to specific embodiments disclosed in these Examples, which are for purposes of illustration only, since alternative methods can be utilized to obtain similar results.

EMBODIMENTS

[0210] Embodiments include embodiments P1 to P41 following.

Embodiment P1

[0211] A method of detecting methylation or unmethylation of a thyroid nodule DNA of a subject, the method comprising: (i) isolating DNA from a thyroid nodule of said subject thereby forming isolated thyroid nodule DNA, (ii) contacting said isolated thyroid nodule DNA with sodium bisulfite thereby forming a reacted thyroid nodule DNA, (iii) detecting the presence or absence of uracil in said reacted thyroid nodule DNA at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of said thyroid nodule DNA of said subject.

Embodiment P2

[0212] The method of embodiment P1, further comprising determining alteration in methylation at a plurality of methylation sites set forth in Table 1.

Embodiment P3

[0213] The method of embodiment P2, said alteration comprises increase or loss of uracil level at said plurality of methylation sites.

Embodiment P4

[0214] The method of embodiment P3, wherein said uracil level is above a threshold as set forth in Table 2.

Embodiment P5

[0215] The method of embodiment P3, wherein said uracil level is above a threshold as set forth in Table 3.

Embodiment P6

[0216] The method of embodiment P3, wherein said uracil level is below a threshold as set forth in Table 4.

Embodiment P7

[0217] The method of embodiment P3, wherein said subject is a candidate thyroid cancer patient.

Embodiment P8

[0218] The method of embodiment P4, wherein said above threshold identifies said thyroid nodule as a cancerous thyroid nodule.

Embodiment P9

[0219] The method of embodiment P5, wherein said above threshold identifies said thyroid nodule as a benign thyroid nodule.

Embodiment P10

[0220] The method of embodiment P6, wherein said below threshold identifies said thyroid nodule as a benign thyroid nodule.

Embodiment P11

[0221] The method of one of the above embodiments, wherein said thyroid nodule is a specimen obtained by biopsy or by surgical resection of said subject.

Embodiment P12

[0222] The method of embodiment P11, wherein said subject has undergone thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and administration of an active agent.

Embodiment P13

[0223] The method of embodiment P12, wherein said active agent is chosen from Cabozantinib-S-Malate, Caprelsa (Vandetanib), Cometriq (Cabozantinib-S-Malate), Doxorubicin Hydrochloride, Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate), Nexavar (Sorafenib Tosylate). Sorafenib Tosylate, and Vandetanib.

Embodiment P14

[0224] A method of determining a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof, said method comprising: (i) isolating DNA from a thyroid nodule of said subject thereby forming isolated thyroid nodule DNA; (ii) contacting said isolated thyroid nodule DNA with sodium bisulfite thereby forming a reacted thyroid nodule DNA; and (iii) detecting the presence or absence of uracil in said reacted thyroid nodule DNA at a methylation site set forth in Table 1: thereby determining said thyroid cancer in said subject.

Embodiment P15

[0225] The method of embodiment P14, further comprising selecting a subject that has or is at risk for developing thyroid cancer.

Embodiment P16

[0226] The method of embodiment P14, further comprising determining alteration in methylation at a plurality of methylation sites set forth in Table 1.

Embodiment P17

[0227] The method of embodiment P16, said alteration comprises increase or loss of uracil level at said plurality of methylation sites.

Embodiment P18

[0228] The method of embodiment P17, wherein said uracil level is above a threshold as set forth in Table 2.

Embodiment P19

[0229] The method of embodiment P17, wherein said uracil level is above a threshold as set forth in Table 3.

Embodiment P20

[0230] The method of embodiment P17, wherein said uracil level is below a threshold as set forth in Table 4.

Embodiment P21

[0231] The method of embodiment P17, wherein said subject is a candidate thyroid cancer patient.

Embodiment P22

[0232] The method of embodiment P18, wherein said above threshold identifies said thyroid nodule as a cancerous thyroid nodule.

Embodiment P23

[0233] The method embodiment P19, wherein said above threshold identifies said thyroid nodule as a benign thyroid nodule.

Embodiment P24

[0234] The method of embodiment P20, wherein said below threshold identifies said thyroid nodule as a benign thyroid nodule.

Embodiment P25

[0235] The method of embodiments P14-P24, wherein said thyroid nodule is a specimen obtained by biopsy or by surgical resection of said subject.

Embodiment P26

[0236] The method of embodiment P25, wherein said subject has undergone thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and administration of an active agent, before said determination.

Embodiment P27

[0237] The method of embodiment P26, wherein said active agent is chosen from Cabozantinib-S-Malate, Caprelsa (Vandetanib), Cometriq (Cabozantinib-S-Malate), Doxorubicin Hydrochloride. Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate), Nexavar (Sorafenib Tosylate). Sorafenib Tosylate, and Vandetanib.

Embodiment P28

[0238] A method of treating thyroid cancer in a subject determined by the method as set forth in embodiment P22, comprising administering to said subject an active agent for treating thyroid cancer.

Embodiment P29

[0239] The method of embodiment P28, wherein said subject has undergone surgery, radiation therapy, radioactive iodine therapy, chemotherapy, or thyroid hormone therapy, before said detection of embodiment 14 at (iii).

Embodiment P30

[0240] The method of embodiment P29, wherein said active agent is chosen from Cabozantinib-S-Malate. Caprelsa (Vandetanib), Cometriq (Cabozantinib-S-Malate), Doxorubicin Hydrochloride, Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate), Nexavar (Sorafenib Tosylate), Sorafenib Tosylate, and Vandetanib.

Embodiment P31

[0241] The method of one of above embodiments, wherein said subject has or is at risk of papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, or anaplastic thyroid cancer.

Embodiment P32

[0242] A deoxyribonucleic acid 5 to 100 nucleotides in length comprising a uracil-containing sequence identical to at least a 5 contiguous nucleotide sequence within a sequence chosen from SEQ ID NO:1 to SEQ ID NO:550.

Embodiment P33

[0243] The deoxyribonucleic acid of embodiment P32 identical to 5-10, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-110, 110-120, 120-130, 130-140, 140-150, 150-160, 160-170, 170-180, 180-190, or 190-200 of contiguous nucleotide sequence of said sequence chosen from SEQ ID NO:1 to SEQ ID NO:550.

Embodiment P34

[0244] The deoxyribonucleic acid of embodiment P32 or P33, wherein said sequence comprises a methylation site set forth in Table 2.

Embodiment P35

[0245] The deoxyribonucleic acid of embodiment P34, wherein a plurality of methylation sites set forth in Table 2 are methylated or unmethylated.

Embodiment P36

[0246] A deoxyribonucleic acid chosen from SEQ ID NO:551 to SEQ ID NO:782, wherein said nucleic acid is hybridized to a complementary DNA sequence comprising uridine or cytosine.

Embodiment P37

[0247] The deoxyribonucleic acid of embodiment P36, further comprising an enzyme in a complex with said hybridized complementary DNA sequence.

Embodiment P38

[0248] The deoxyribonucleic acid of embodiment P37, wherein said enzyme is Taq polymerase.

Embodiment P39

[0249] A kit comprising 322 nucleic acids each independently comprising SEQ ID NO:551 to SEQ ID NO:782, wherein said nucleic acids do not simultaneously comprise the same SEQ ID NO:551 to SEQ ID NO:782.

Embodiment P40

[0250] The kit according to embodiment P39, further comprising: enzymes, reagents for deamination of cytosine, buffers, vials, plasmid vectors, control DNA, devices for collecting thyroid tissue samples, reagents for isolating DNA, reagents for labeling DNA, or any combinations thereof.

Embodiment P41

[0251] The kit according to embodiment P40, wherein the enzymes are selected from the group consisting of: thermostable DNA polymerase enzymes, restriction enzymes, and combination thereof.

[0252] Further embodiments include embodiments 1-58 following.

Embodiment 1

[0253] A method of detecting methylation or unmethylation of a thyroid nodule DNA molecule of a subject, the method comprising: (i) isolating a thyroid nodule DNA molecule from a thyroid nodule of said subject thereby forming an isolated thyroid nodule DNA molecule. (ii) contacting said isolated thyroid nodule DNA molecule with a bisulfite salt thereby forming a reacted thyroid nodule DNA molecule, (iii) detecting the presence or absence of uracil in said reacted thyroid nodule DNA molecule at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of said thyroid nodule DNA molecule of said subject.

Embodiment 2

[0254] The method of embodiment 1, further comprising detecting the presence or absence of uracil in said reacted thyroid nodule DNA molecule at a plurality of methylation sites set forth in Table 1, wherein said methylation site forms a part of said plurality of methylation sites.

Embodiment 3

[0255] The method of embodiment 1, the method further comprising: (i) isolating a plurality of thyroid nodule DNA molecules from said thyroid nodule of said subject thereby forming a plurality of isolated thyroid nodule DNA molecules, wherein said isolated thyroid nodule DNA molecule forms part of said plurality of isolated thyroid nodule DNA molecules, (ii) contacting said plurality of isolated thyroid nodule DNA molecules with said bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, wherein said reacted thyroid nodule DNA molecule forms part of said plurality of reacted thyroid nodule DNA molecules, (iii) detecting the level of reacted thyroid nodule DNA molecules in said plurality of reacted thyroid nodule DNA molecules having a uracil at a methylation site set forth in Table 1, thereby detecting the level of methylation or unmethylation in said plurality of thyroid nodule DNA molecules of said subject.

Embodiment 4

[0256] The method of embodiment 3, further comprising determining the level of uracil in said reacted thyroid nodule DNA molecule at a plurality methylation sites set forth in Table 1, wherein said methylation site forms a part of said plurality of methylation sites.

Embodiment 5

[0257] The method of embodiment 4, wherein said uracil level is above a threshold as set forth in Table 2.

Embodiment 6

[0258] The method of embodiment 4, wherein said uracil level is above a threshold as set forth in Table 3.

Embodiment 7

[0259] The method of embodiment 4, wherein said uracil level is below a threshold as set forth in Table 4.

Embodiment 8

[0260] The method of one of the above embodiments, wherein said subject is suspected of having thyroid cancer.

Embodiment 9

[0261] The method of one of the above embodiments, wherein said thyroid nodule is a specimen obtained by biopsy or by surgical resection of said subject.

Embodiment 10

[0262] The method of one of the above embodiments, wherein said subject has undergone thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and/or administration of an active agent.

Embodiment 11

[0263] The method of embodiment 10, wherein said active agent is chosen from Cabozantinib-S-Malate, Caprelsa (Vandetanib), Cometriq (Cabozantinib-S-Malate). Doxorubicin Hydrochloride. Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate), Nexavar (Sorafenib Tosylate), Sorafenib Tosylate, and/or Vandetanib.

Embodiment 12

[0264] A method of detecting a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof, said method comprising:

[0265] (i) isolating a thyroid nodule DNA molecule from a thyroid nodule of said subject thereby forming an isolated thyroid nodule DNA molecule;

[0266] (ii) contacting said isolated thyroid nodule DNA molecule with a bisulfite salt thereby forming a reacted thyroid nodule DNA molecule; and

[0267] (iii) detecting the presence or absence of uracil in said reacted thyroid nodule DNA molecule at a methylation site set forth in Table 1; thereby detecting said thyroid cancer in said subject.

Embodiment 13

[0268] The method of embodiment 12, wherein said subject (a) is a woman; (b) is about 20 to about 55 years old; (c) has a mutated Ret Proto-Oncogene; (d) has a grandparent, parent, or sibling who has been diagnosed with thyroid cancer; (e) self-identifies as being Caucasian or Asian; and/or (f) has or has had breast cancer.

Embodiment 14

[0269] The method of embodiment 12, further comprising detecting the presence or absence of uracil in said reacted thyroid nodule DNA molecule at a plurality of methylation sites set forth in Table 1, wherein said methylation site forms a part of said plurality of methylation sites.

Embodiment 15

[0270] The method of embodiment 12, the method further comprising: (i) isolating a plurality of thyroid nodule DNA molecules from said thyroid nodule of said subject thereby forming a plurality of isolated thyroid nodule DNA molecules, wherein said isolated thyroid nodule DNA molecule forms part of said plurality of isolated thyroid nodule DNA molecules, (ii) contacting said plurality of isolated thyroid nodule DNA molecules with said bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, wherein said reacted thyroid nodule DNA molecule forms part of said plurality of reacted thyroid nodule DNA molecules, (iii) detecting the level of reacted thyroid nodule DNA molecules in said plurality of reacted thyroid nodule DNA molecules having a uracil at a methylation site set forth in Table 1; thereby detecting said thyroid cancer in said subject.

Embodiment 16

[0271] The method of embodiment 15, further comprising determining the level of uracil in said reacted thyroid nodule DNA molecule at a plurality methylation sites set forth in Table 1, wherein said methylation site forms a part of said plurality of methylation sites.

Embodiment 17

[0272] The method of embodiment 16, wherein said uracil level is above a threshold as set forth in Table 2.

Embodiment 18

[0273] The method of embodiment 16, wherein said uracil level is above a threshold as set forth in Table 3.

Embodiment 19

[0274] The method of embodiment 16, wherein said uracil level is below a threshold as set forth in Table 4.

Embodiment 20

[0275] The method of one of the above embodiments, wherein said subject is suspected of having thyroid cancer.

Embodiment 21

[0276] The method of one of the above embodiments, wherein said thyroid nodule is a specimen obtained by biopsy or by surgical resection of said subject.

Embodiment 22

[0277] The method of one of the above embodiments, wherein said subject has undergone thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and administration of an active agent, before said determination.

Embodiment 23

[0278] The method of embodiment 22, wherein said active agent is chosen from Cabozantinib-S-Malate, Caprelsa (Vandetanib), Cometriq (Cabozantinib-S-Malate), Doxorubicin Hydrochloride, Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate), Nexavar (Sorafenib Tosylate), Sorafenib Tosylate, and.

Embodiment 24

[0279] A method of treating thyroid cancer in a subject determined by the method as set forth in any of embodiments 12 to 23, comprising administering to said subject an active agent for treating thyroid cancer.

Embodiment 25

[0280] The method of embodiment 24, wherein said subject has undergone surgery, radiation therapy, radioactive iodine therapy, chemotherapy, or thyroid hormone therapy, before said detection of claim 12 at (iii).

Embodiment 26

[0281] The method of embodiment 25, wherein said active agent is chosen from Cabozantinib-S-Malate. Caprelsa (Vandetanib), Cometriq (Cabozantinib-S-Malate). Doxorubicin Hydrochloride. Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate), Nexavar (Sorafenib Tosylate). Sorafenib Tosylate, and Vandetanib.

Embodiment 27

[0282] The method of one of the above embodiments, wherein said subject has or is at risk of papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, or anaplastic thyroid cancer.

Embodiment 28

[0283] The method of one of the above embodiments, wherein said bisulfite salt is sodium bisulfite.

Embodiment 29

[0284] The method of one of the above embodiments, further comprising determining a papillary thyroid carcinoma (PTC) methylation alteration score for said subject, wherein the PTC methylation alteration score is equal to: the number of methylation sites in Table 1 having a uracil level equal to or greater than the corresponding threshold level set forth in Table 2.

Embodiment 30

[0285] The method of one of the above embodiments, further comprising determining a benign thyroid nodule (BTN) methylation alteration score for said subject, wherein the BTN methylation alteration score is equal to:

[0286] (a) the number of methylation sites in Table 1 having a uracil level equal to or greater than the corresponding threshold level set forth in Table 3;

[0287] (b) the number of methylation sites in Table 1 having a uracil level equal to or less than the corresponding threshold level set forth in Table 4; or

[0288] (c) the number of methylation sites in Table 1 having a uracil level equal to or greater than the corresponding threshold level set forth in Table 3 plus the number of methylation sites in Table 1 having a uracil level equal to or less than the corresponding threshold level set forth in Table 4.

Embodiment 31

[0289] The method of embodiment 29, further comprising calculating a Composite Cancer Risk Score for said subject.

Embodiment 32

[0290] The method of embodiment 31, wherein said Composite Cancer Risk Score for said subject equals:

[0291] [the PTC methylation alteration score for said subject]/[BTN methylation alteration score for said subject].

Embodiment 33

[0292] The method of embodiment 31, wherein said Composite Cancer Risk Score for said subject equals:

[0293] [(the PTC methylation alteration score for said subject)+1]/[(BTN methylation alteration score for said subject)+1].

Embodiment 34

[0294] The method of one of embodiments 29 to 33, wherein said subject is identified as being at risk of developing thyroid cancer or diagnosed as having thyroid cancer if (a) the PTC methylation alteration score for said subject is at least 5, 6, 7, 8, 9, or 10; (b) the BTN methylation alteration score for said subject is at least 5, 6, 7, 8, 9, or 10; and/or (c) the Composite Cancer Risk Score for said subject is at least about 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3.0.

Embodiment 35

[0295] The method of one of embodiments 29 to 33, wherein said subject is treated for thyroid cancer or directed to receive additional screening for thyroid cancer if (a) the PTC methylation alteration score for said subject is at least 5, 6, 7, 8, 9, or 10; (b) the BTN methylation alteration score for said subject is at least 5, 6, 7, 8, 9, or 10; and/or (c) the Composite Cancer Risk Score for said subject is at least about 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3.0.

Embodiment 36

[0296] A deoxyribonucleic acid at least 5 to 100 nucleotides in length comprising a uracil-containing sequence that is identical to a sequence of at least a 5 contiguous nucleotides within a sequence chosen from SEQ ID NO: 1 to SEQ ID NO:550.

Embodiment 37

[0297] The deoxyribonucleic acid of embodiment 36, comprising a uracil-containing sequence that is identical to a sequence of at least 5-10, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70.70-80, 80-90, 90-100, 100-110, 110-120, 120-130, 130-140, 140-150, 150-160, 160-170, 170-180, 180-190, or 190-200 contiguous nucleotides within said sequence chosen from SEQ ID NO:1 to SEQ ID NO:550.

Embodiment 38

[0298] The deoxyribonucleic acid of embodiment 36 or 37, wherein said sequence comprises a methylation site set forth in Table 1.

Embodiment 39

[0299] The deoxyribonucleic acid of one of embodiments 36 to 38, wherein a plurality of methylation sites set forth in Table 1 contain a uracil or a cytosine.

Embodiment 40

[0300] A deoxyribonucleic acid chosen from SEQ ID NO:551 to SEQ ID NO:782, wherein said nucleic acid is hybridized to a complementary DNA sequence comprising uridine or cytosine.

Embodiment 41

[0301] The deoxyribonucleic acid of embodiment 40, further comprising an enzyme in a complex with said hybridized complementary DNA sequence.

Embodiment 42

[0302] The deoxyribonucleic acid of embodiment 41, wherein said enzyme is Taq polymerase.

Embodiment 43

[0303] A kit comprising a plurality of nucleic acids each independently comprising SEQ ID NO:551 to SEQ ID NO:782, wherein each nucleic acid of said plurality is unique.

Embodiment 44

[0304] The kit according to embodiment 43, further comprising: an enzyme, a reagent for deamination of cytosine, a buffer, a vial, a plasmid vector, a control DNA, a device for collecting a thyroid tissue sample, a reagent for isolating DNA, a reagent for labeling DNA, or any combination thereof.

Embodiment 45

[0305] The kit according to embodiment 44, wherein the enzyme comprises a thermostable DNA polymerase enzyme and/or a restriction enzyme.

Embodiment 46

[0306] A system for detecting methylation or unmethylation of a thyroid nodule deoxyribonucleic acid (DNA) of a subject, the system comprising:

[0307] at least one processor; and

[0308] at least one memory including program code which when executed by the at least one memory provides operations comprising:

[0309] isolating a thyroid nodule DNA molecule from a thyroid nodule of said subject thereby forming an isolated thyroid nodule DNA molecule;

[0310] contacting said isolated thyroid nodule DNA molecule with a bisulfite salt thereby forming a reacted thyroid nodule DNA molecule;

[0311] detecting the presence or absence of uracil in said reacted thyroid nodule DNA molecule at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of said thyroid nodule DNA molecule of said subject;

[0312] generating a diagnosis for said subject based at least in part on the presence or absence of uracil in said reacted thyroid nodule DNA molecule at the methylation site set forth in Table 1; and

[0313] providing, via a user interface, the diagnosis for said subject.

Embodiment 47

[0314] The system of embodiment 46, wherein the system is further configured to detect the presence or absence of uracil in said reacted thyroid nodule DNA molecule at a plurality of methylation sites set forth in Table 1, wherein said methylation site forms a part of said plurality of methylation sites.

Embodiment 48

[0315] The system of embodiment 46, wherein the system is further configured to: (i) isolate a plurality of thyroid nodule DNA molecules from said thyroid nodule of said subject thereby forming a plurality of isolated thyroid nodule DNA molecules, wherein said isolated thyroid nodule DNA molecule forms part of said plurality of isolated thyroid nodule DNA molecules, (ii) contact said plurality of isolated thyroid nodule DNA molecules with said bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, wherein said reacted thyroid nodule DNA molecule forms part of said plurality of reacted thyroid nodule DNA molecules, (iii) detect the level of reacted thyroid nodule DNA molecules in said plurality of reacted thyroid nodule DNA molecules having a uracil at a methylation site set forth in Table 1, thereby detecting the level of methylation or unmethylation in said plurality of thyroid nodule DNA molecules of said subject.

Embodiment 49

[0316] The system of embodiment 48, wherein the system is further configured to detect the level of uracil in said reacted thyroid nodule DNA molecule at a plurality methylation sites set forth in Table 1, wherein said methylation site forms a part of said plurality of methylation sites.

Embodiment 50

[0317] The system of embodiment 49, wherein said uracil level is above a threshold as set forth in Table 2.

Embodiment 51

[0318] The system of embodiment 49, wherein said uracil level is above a threshold as set forth in Table 3.

Embodiment 52

[0319] The system of embodiment 49, wherein said uracil level is below a threshold as set forth in Table 4.

Embodiment 53

[0320] The system of embodiment 49, wherein said subject is a candidate thyroid cancer patient.

Embodiment 54

[0321] The system of one of embodiments 46 to 53, wherein said thyroid nodule is a specimen obtained by biopsy or by surgical resection of said subject.

Embodiment 55

[0322] The system of one of embodiments 46 to 54, wherein said subject has undergone thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and/or administration of an active agent.

Embodiment 56

[0323] The system of embodiment 55, wherein said active agent is chosen from Cabozantinib-S-Malate, Caprelsa (Vandetanib), Cometriq (Cabozantinib-S-Malate), Doxorubicin Hydrochloride, Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate), Nexavar (Sorafenib Tosylate), Sorafenib Tosylate, and Vandetanib.

Embodiment 57

[0324] The system of one of embodiments 46 to 56, wherein the system is further configured to:

[0325] formulate, based at least in part on the diagnosis, a treatment plan for said subject; and

[0326] provide, via the user interface, the treatment plan.

Embodiment 58

[0327] The system of embodiment 57, wherein the treatment plan includes one or more of thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and administration of an active agent.

EXAMPLES

Example 1

[0328] Human frozen specimens were blindly evaluated by a pathologist. In the study, 28 benign nodules and 40 thyroid cancer specimens were analyzed.

DNA Methylation Profiling

[0329] Genomic DNA was isolated by using a standard phenol/chloroform extraction approach followed by ethanol precipitation. Further, genomic DNA underwent Reduced Representation Bisulfite Sequencing (RRBS) procedure. RRBS DNA amplicons were paired-end sequenced by using Hiseq 2500 (Illumina). For each sample, at least 15 million aligned reads were obtained. BTN and PTC specific signatures were determined based on cytosines which are characterized by at least 5 sequencing reads in each sample.

Identification of BTN Specific and PTC Specific DNA Methylation Changes

[0330] DNA methylation patterns were analyzed in 114 thyroid specimens including 28 benign nodules, 40 thyroid cancer, and 46 adjacent normal thyroid tissues, to identify the presence of thyroid cancer specific and benign nodule specific signatures. After genome alignment, a search was performed for DNA regions which have BTN or PTC specific alterations. For identification of a DNA region with a BTN specific loss of DNA methylation, DNA regions were identified which had a DNA methylation level in at least 6 out 28 that was at least 2-fold less than the level of methylation in the same DNA region any analyzed PTC specimen, where the lowest value of DNA methylation at this DNA region among all PTC specimens is 20% or higher (FIG. 1A). For identification of DNA regions with BTN specific DNA methylation accumulation, the following criteria were used; a level of DNA methylation in an individual BTN that is at least 2-fold higher than the level of DNA methylation in the same DNA region in any analyzed PTC; where the value of DNA methylation of analyzed BTN specimen is at least 20% or more greater (FIG. 1B). The BTN signature includes DNA regions which were affected by DNA methylation loss in at least 6 out 28 analyzed BTN samples and regions which were affected by DNA methylation accumulation in at least 6 out 28 analyzed BTN samples.

[0331] Further, regions were determined which undergo PTC specific DNA methylation alterations. The criteria for the identification of DNA regions with a PTC specific loss of DNA methylation, was: a level of DNA methylation in 6 out of 46 PTC that is 2-fold less than in any analyzed adenoma and any normal matching tissue, where the lowest value of DNA methylation in the region among all non-malignant specimens is 20% or higher. The criteria for the identification of DNA regions with PTC specific DNA methylation accumulation was a level of DNA methylation in an individual PTC that is at least 2-fold higher than the level of methylation in any analyzed adenoma and normal matching tissue, where the value of DNA methylation in analyzed PTC sample should be 20% or higher. There were no DNA regions that were affected by DNA methylation accumulation in at least 6 PTC out 46 analyzed PTC. Therefore, the PTC specific DNA methylation signatures contain only DNA regions which are affected by DNA methylation loss in at least 6 out 46 analyzed PTC.

[0332] The total number of identified DNA regions which fall in PTC specific or BTN specific signature is 258, which comprises DNA methylation information for 364 cytosines (FIG. 2A). There are 230 cytosines which characterize the PTC signature and 134 cytosines characterizing the BTN signature.

[0333] Evaluation of the cancer specific and benign specific changes revealed that 10 out of 40 thyroid cancer specimens are characterized by few (less than 5) or no cancer specific changes, and 4 out 28 benign nodules indicated very few (less than 5) benign specific changes (FIG. 2A). Since the approach described herein is based on the identification of the tissue specific alterations, these specimens were determined to be "epigenetically indeterminate."

[0334] For specimens with a determinate epigenetic state, clustering analysis revealed a strict separation of thyroid cancer from benign nodules based on DNA methylation levels of cytosines associated with benign and cancer scores (FIG. 2B). Thus, the use of benign and cancer scores can provide a unique thyroid nodule diagnostic tool.

Development of Diagnostic Panel Based on BTN/PTC Signature Scores.

[0335] The data disclosed herein demonstrates that analysis of DNA methylation of one or more of 258 DNA regions can provide substantial information regarding a presence of malignancy in thyroid samples. Therefore, DNA methylation analysis within BTN and PTC signature can be used as a PTC diagnostic tool. According to the data, PTC diagnosis can be made by using both BTN and PTC signatures. Each signature can be a score based on the number of specific alterations within the signature for each individual sample. For example, the number of BTN specific alterations within BTN signature DNA regions reflects a BTN signature score. At the same time, the number of PTC specific alterations for DNA regions within PTC signature group indicates PTC signature score.

[0336] In order to validate the approach disclosed herein and estimate an accuracy of the proposed signatures, a statistical analysis was performed based on the leave-one-out-cross-validation technique. Specifically, cancer and benign scores were determined for each individual nodule by using benign and cancer signatures which were developed based on DNA methylation patterns of the rest of samples excluding the testing sample. In order to predict benign and cancer scores for 68 nodules, 68 benign and cancer unique predictive signatures were developed.

[0337] After cross-validation. DNA methylation signatures (score >=5) were observed in 80% (32 out 40) of thyroid cancers and 82% (23 out 28) of benign nodules (FIG. 3A). These specimens with a determinate epigenetic state were used for the further analysis.

[0338] According to the cross-validation observations, both, benign and malignant diagnostic scores provided accurate results for thyroid nodule diagnostics (FIG. 3A). However, a combining of benign and malignant scores into a cancer risk score is associated with even higher diagnostic performance. The cancer risk score was calculated using the following equation: Cancer Risk Score=(cancer score+1)/(benign score+1)

[0339] According to the data herein, specimens with cancer risk score above 2.6 represent thyroid cancer and specimens with cancer score below 2.6 are benign nodules. Based on these criteria, all 23 nodules were correctly diagnosed as benign and 30 out 32 thyroid malignancies were diagnosed as a cancer (FIG. 3B). Therefore, the test had a specificity of 100% and a sensitivity of 94%, with a 100% positive predictive value (PPV) and a 92% negative predictive value (NPV). These data suggest that DNA methylation analysis of 258 DNA regions in thyroid specimens can serve as a potential diagnostic tool for the determination of malignancy.

[0340] An algorithm for performing a thyroid nodule diagnostic evaluation is shown in FIG. 3C. Specimens with benign and malignant signatures are associated with indeterminate epigenetic state and were excluded from the study. Specimens with a cancer risk score above 2.6 are considered to be malignant, and thyroid nodules with a cancer risk score below 2.6 are considered to be benign.

[0341] This scoring approach clearly differentiates benign from malignant specimens. These data suggest that DNA methylation analysis of 258 DNA regions in thyroid specimens, including potentially FNA specimens, can serve as a diagnostic tool for the determination of malignancy.

[0342] The data indicates that malignancy of thyroid specimens can be determined by DNA methylation pattern analysis of one or more of 258 different DNA regions.

Sequence CWU 1

1

7821300DNAArtificial SequenceSynthetic polynucleotide 1tuuttaguuu tuygtggygu uagagttggt tguutuagta gygygtguuu auuygguuua 60aagutgttut guagutggtu autgtgggag aagagautgg aaaagttuaa aggtggagag 120gygguagyga tutggaguau ttttuyguay gutgtaauuu utgagaagaa auaaagagga 180aaygaggutg tttagataat uuyggguuut ggtguttgua tttagaaaaa ttagguuutu 240ttgaaaaatt auagaattat gutguuagtg tuaggttuuu agataatgat gtgtutgtgt 3002300DNAArtificial SequenceSynthetic polynucleotide 2uauagauaua tuattatutg ggaauutgau autgguagua taattutgta atttttuaag 60aggguutaat ttttutaaat guaaguauua ggguuyggga ttatutaaau aguutygttt 120uututttgtt tuttutuagg ggttauagyg tgyggaaaag tgutuuagat ygutguyguu 180tutuuauutt tgaauttttu uagtututtu tuuuauagtg auuagutgua gaauaguttt 240ggguygggtg gguaygygut autgagguaa uuaaututgg yguuayggag ggutaaggau 3003300DNAArtificial SequenceSynthetic polynucleotide 3gggtgauuag tguuautaaa aguagagutt gagtttautu tuataauuat yggutgtggg 60uuagauattt ggutgutttg uagguagauu agguttuuyg gtgagtuatg utguttaaaa 120tgutgtutgg gaayguagag aaagtutaaa yguuaagayg utgaggauag uuuyguaggt 180ggautguuat guuyggutyg guuuuttttt ggtuuuuaga gtggauuutt utuutuuuua 240uagaggggag guatutgatg gtgguttuag uagauaauut ggagaagaau uautuagggt 3004300DNAArtificial SequenceSynthetic polynucleotide 4auuutgagtg gttuttutuu aggttgtutg utgaaguuau uatuagatgu utuuuututg 60tggggaggag aagggtuuau tutggggauu aaaaaggggu ygaguygggu atgguagtuu 120auutgygggg utgtuutuag ygtuttggyg tttagauttt ututgygttu uuagauagua 180ttttaaguag uatgautuau ygggaaguut ggtutguutg uaaaguaguu aaatgtutgg 240uuuauaguyg atggttatga gagtaaautu aagututgut tttagtggua utggtuauuu 3005300DNAArtificial SequenceSynthetic polynucleotide 5cagutgggga ggggauaggg taggtggutg uagaaggggg utgggttgag gtutuaggtg 60uagaygagga ggggutgggy ggagggggtg aggaggggag uygggutggg gguyggggyg 120utgutggggt uuuuutuuyg uuuygggauy gtuygututt guuuagauuy gtyggtaaau 180agayguygtg atgtuayggg yguygutgau utgtggutga auuyggagut gtaaatgaga 240tguaaggtgu uaguaguutu ygguyguagg guutaygagu uauaygygut uutuyguygg 3006300DNAArtificial SequenceSynthetic polynucleotide 6uyggyggagg agygygtgtg gutygtaggu uutgygguyg gaggutgutg guauuttgua 60tutuatttau agutuygggt tuaguuauag gtuagyggyg uuygtgauat uayggygtut 120gtttauygay gggtutgggu aagagyggay ggtuuygggg ygggaggggg auuuuaguag 180yguuuygguu uuuaguuygg utuuuutuut uauuuuutuy guuuaguuuu tuutygtutg 240uauutgagau utuaauuuag uuuuuttutg uaguuauuta uuutgtuuuu tuuuuagutg 3007300DNAArtificial SequenceSynthetic polynucleotide 7ttttutgtaa aatgggguyg uuuauaaaau tuataauaaa gtgttgaggt tuygauaagu 60ygaaauutgt gaaaaguttg tgtaaauutu agagutgtau atggatggtt gaaggatuta 120tttygauagu tuyggggagu ygtgggaggg aagutgaygg yggututtgu tgttutuuta 180uutuuuaguu utuuygaaga ututgaguag uutggagatu aaaggtgatt gggguutgut 240gguatggagg uygggutygg uagaauutgu ttuuygguuu uutguuuauu tuuuauuuau 3008300DNAArtificial SequenceSynthetic polynucleotide 8gtgggtggga ggtggguagg ggguygggaa guaggttutg uygaguuygg uutuuatguu 60aguagguuuu aatuauuttt gatutuuagg utgutuagag tuttygggag ggutgggagg 120taggagaaua guaagaguyg uygtuagutt uuutuuuayg gutuuuygga gutgtygaaa 180tagatuuttu aauuatuuat gtauagutut gaggtttaua uaaguttttu auaggtttyg 240guttgtygga auutuaauau tttgttatga gttttgtggg ygguuuuatt ttauagaaaa 3009300DNAArtificial SequenceSynthetic polynucleotide 9tgaguagtgt ttuagyguuu agagagauau tgtggagaag gtuuauuagg atguutauut 60guuttauaua agaguutaau tttgguauau utgtgguaua uutgtggaga gutgttutgg 120uuuyggttgt utgguagguu tgggutautu ygaguagggg aautggggua uagtggutgu 180auutuyggut atauuutggt ttttuuagtt uutgatguuy guuuutuagg tgguaguatg 240aggtgautua gggauagayg uuuttatygt gayguaagtu uaguuuuuag tggaguuuut 30010300DNAArtificial SequenceSynthetic polynucleotide 10aggggutuua utgggggutg gauttgygtu aygataaggg ygtutgtuuu tgagtuauut 60uatgutguua uutgaggggy ggguatuagg aautggaaaa auuagggtat aguyggaggt 120guaguuautg tguuuuagtt uuuutgutyg gagtaguuua gguutguuag auaauygggg 180uuagaauagu tutuuauagg tgtguuauag gtgtguuaaa gttaggutut tgtgtaaggu 240aggtagguat uutggtggau uttutuuaua gtgtututut gggygutgaa auautgutua 30011300DNAArtificial SequenceSynthetic polynucleotide 11tuttgtaaaa ttuuagaguu aggtatauuu aattutguaa ygtggtagut guatgautgt 60auaagtuuut taauaguauy ggguutuagt gauatuatut gttaaatggg ttggtgatga 120taatggtuag uatttatgga ggaguuuaua yggtgutaag tgutttauau atatuaguta 180autgaatuut uautgutguu aatgagauag gtautattga atuagagguu yggagagagu 240tuuaygyggt tggtuataut ggtgaagagu ttggttuaat guutggtgaa ututygguau 30012300DNAArtificial SequenceSynthetic polynucleotide 12gtguygagag ttuauuaggu attgaauuaa gututtuauu agtatgauua auygygtgga 60gutututuyg gguututgat tuaatagtau utgtutuatt gguaguagtg aggattuagt 120tagutgatat gtgtaaagua uttaguauyg tgtgggutuu tuuataaatg utgauuatta 180tuatuauuaa uuuatttaau agatgatgtu autgagguuy ggtgutgtta agggauttgt 240auagtuatgu agutauuayg ttguagaatt gggtatauut ggututggaa ttttauaaga 30013300DNAArtificial SequenceSynthetic polynucleotide 13tuyggaguua gtgaauttgt gatuyggagu uagttaautt uauagutaat gtgutgagua 60guattuuagu uagygtutga aguuagagua gggaggygga yggguuuuag gagttygagg 120tuygggaagu ygaaguauua uuaaautgag ygaggttuua aututuuutu uuaggaggtu 180yggutguutu uuauuaguag uuuaauuaua gggtuutgut uuagaygtta utattttutu 240tttttuagtg tgtuuaguag uaauutygau tguuaauaau aaygtgaaaa ataautguag 30014300DNAArtificial SequenceSynthetic polynucleotide 14utguagttat ttttuaygtt gttgttggua gtygaggttg utgutggaua uautgaaaaa 60gagaaaatag taaygtutgg aguaggauuu tgtggttggg utgutggtgg gagguaguyg 120gauutuutgg gagggagagt tggaauutyg utuagtttgg tggtguttyg guttuuygga 180uutygaautu utgggguuyg tuyguutuuu tgututggut tuagaygutg gutggaatgu 240tgutuaguau attagutgtg aagttaautg gutuyggatu auaagttuau tggutuygga 30015300DNAArtificial SequenceSynthetic polynucleotide 15ttguuaaaau tggaaguaau uaagatguuu utuaaaaggt gaatggaggu uaggtgyggt 60ggutuayguy gataatuuua guautttggg aggutgaggu aggtggatua uttgagatua 120ygagtttgag auuaguuygg uuaauatggy gaaauuuygt ututautaaa aatautaaga 180ttaauygggy gtggtgguay gtguutgtta tuuuagutau ttgggaagut gagguaggua 240aattguttga auutgggagg tggaggtuau agtgaguuaa gattgtguua utguautuua 30016300DNAArtificial SequenceSynthetic polynucleotide 16tggagtguag tgguauaatu ttggutuaut gtgauutuua uutuuuaggt tuaaguaatt 60tguutguutu aguttuuuaa gtagutggga taauagguay gtguuauuay guuyggttaa 120tuttagtatt tttagtagag ayggggttty guuatgttgg uygggutggt utuaaautyg 180tgatutuaag tgatuuauut guutuaguut uuuaaagtgu tgggattaty ggygtgaguu 240auyguauutg guutuuattu auuttttgag ggguatuttg gttguttuua gttttgguaa 30017300DNAArtificial SequenceSynthetic polynucleotide 17ggygggatuy gaguygagau aygtgutgga gyggaguygu ttuutuaygg tyguuaguyg 60uagauaautg auutuuuygg uatygygtty gygguuutgu tgutggutuy ggtgtutygg 120guyggaautu utgtggutuu agygttygyg uygguuautg guuagygutt ggguutyguu 180utguagutuy gggguuatag gguauagutt tagutttgau utuuuygttu uygaaaggay 240guuuaaggyg auutuuuauu uuatuutuuu uaauttutuu uuuatgtuut gygguaautt 30018300DNAArtificial SequenceSynthetic polynucleotide 18agttguygua ggauatgggg gagaagttgg ggaggatggg gtgggaggty guuttgggyg 60tuutttyggg aayggggagg tuaaagutaa agutgtguuu tatgguuuyg gagutguagg 120gygagguuua agygutgguu agtgguyggy gygaaygutg gaguuauagg agttuygguu 180ygagauauyg gaguuaguag uaggguygyg aaygygatgu yggggaggtu agttgtutgy 240ggutggygau ygtgaggaag yggutuygut uuaguaygtg tutyggutyg gatuuyguuu 30019300DNAArtificial SequenceSynthetic polynucleotide 19uuaguaggga agguaguuaa uagatguaga utygututgu utauutgtgg agguyggtga 60gguuaggguu tgttgggaut tgaaauagtg agguaagtgg gtgtgtggtg utgggutuuu 120ygutuaagtt utuuuagygt guuagttuuy ggaguuttat gtguagggtg ttggggaagg 180gygggutgaa tygtgggtgg gagtuttggu tuaaaguuuu aggtgagtgg aggaattggg 240ggyggauutg aagtautgtu ttgaagtgga uutgguaggu ututtgggut tgtguagutg 30020300DNAArtificial SequenceSynthetic polynucleotide 20uagutguaua aguuuaagag guutguuagg tuuauttuaa gauagtautt uaggtuyguu 60uuuaattuut uuautuauut ggggutttga guuaagautu uuauuuayga ttuaguuygu 120uuttuuuuaa uauuutguau ataaggutuy gggaautggu aygutgggag aauttgagyg 180gggaguuuag uauuauauau uuauttguut uautgtttua agtuuuaaua gguuutgguu 240tuauygguut uuauaggtag guagagygag tutguatutg ttggutguut tuuutgutgg 30021300DNAArtificial SequenceSynthetic polynucleotide 21uuagautygu uutuuuuauu yggguutygg autttuauuu uaguttutut utuutgguua 60gtgattauuu auuuuuaatu uuauuuyguu uyguygygua autauutuut uuuttuauuy 120ggautgggau uatuatuuuu autuuautuy guuuagtutg ggautuuauu tguutuutuu 180uuaatuuuau autaatutut guttggtutu ttuututttg guutaatutu tygtutyggu 240ttattgggga ygguuautut uauagtttgg ttuuaaauau uagttuutgg atggattuuu 30022300DNAArtificial SequenceSynthetic polynucleotide 22gggaatuuat uuaggaautg gtgtttggaa uuaaautgtg agagtgguyg tuuuuaataa 60guygagayga gagattaggu uaaagaggaa gagauuaagu agagattagt gtgggattgg 120ggaggaggua ggtggagtuu uagautgggy ggagtggagt ggggatgatg gtuuuagtuy 180gggtgaaggg aggaggtagt tgygyggygg ggyggggtgg gattgggggt gggtaatuau 240tgguuaggag agagaagutg gggtgaaagt uygagguuyg ggtggggagg gygagtutgg 30023300DNAArtificial SequenceSynthetic polynucleotide 23yguagguuyg yguuuygutu uyguuuyguu tguygyguut uuyggggygu uyguattaaa 60gyguatatgu aaguuatgaa ttatuaautg aaaggagtua attauyggut utaaaaayga 120gtgtutgygu tyguagyguu uyggguuatu yguutattta yggagygatu tauuuyguuy 180ggutggggag gggguutygg gagggagaga gayggagaaa yggaguuyga gauygggaga 240gaguyggaga gguagggaut ggagagtutg ggauaygaag gagaggyggg gagagauyga 30024300DNAArtificial SequenceSynthetic polynucleotide 24tyggtututu uuyguututu uttygtgtuu uagaututuu agtuuutguu tutuyggutu 60tutuuyggtu tygggutuyg tttutuygtu tututuuutu uygagguuuu utuuuuaguy 120gggyggggta gatygutuyg taaataggyg gatgguuygg ggygutgyga gyguagauau 180tygtttttag aguyggtaat tgautuuttt uagttgataa ttuatggutt guatatgygu 240tttaatgygg gyguuuyggg aggygyggua ggyggggygg gagyggggyg yggguutgyg 30025300DNAArtificial SequenceSynthetic polynucleotide 25auagtygutg uagggaggay gyggguygtg agaauuyggg gauaguutuu uututtgygg 60tuutguagtu uyggauuuau tgggyggatu agaaagtttg uagggaguua gggautagga 120gauagauaga uagyguaggg auagagaaag yggagggatg uuagaaagau ygagtygggg 180auagauagag agauuuaggg tgagauagag gaagagatau uyggggutga aaayggtggu 240agaaagtgag uaauttaggg agauagaaag agyguagaau tygaaattuy gagguagaga 30026300DNAArtificial SequenceSynthetic polynucleotide 26tututguuty ggaatttyga gttutgygut utttutgtut uuutaagttg utuautttut 60guuauygttt tuaguuuygg gtatututtu ututgtutua uuutgggtut ututgtutgt 120uuuygautyg gtutttutgg uatuuutuyg utttututgt uuutgygutg tutgtutgtu 180tuutagtuuu tggutuuutg uaaautttut gatuyguuua gtgggtuygg gautguagga 240uyguaagagg ggaggutgtu uuygggttut uaygguuygy gtuutuuutg uagygautgt 30027300DNAArtificial SequenceSynthetic polynucleotide 27tuaguutgta uuuyggygut gguutuuaga uaguuaggtg utguutygua yggtuttgut 60tguaggutgg gguatgaagu auuutggtat ttaygutggg attggtutut uautagggtt 120ggggygggut gtggtuauut gguuyggygy guyguagagg utggutuygg agaagauutg 180ggggyguaag autuagaggu uagagggtgu aguygutgut gautuatttg yggayggggy 240ggutgggagg agygutaguu uutgttgtga gygatttgag aguuaggguu aaatutgggt 30028300DNAArtificial SequenceSynthetic polynucleotide 28auuuagattt gguuutggut utuaaatygu tuauaauagg ggutagygut uutuuuaguy 60guuuygtuyg uaaatgagtu aguagyggut guauuututg guututgagt uttgyguuuu 120uaggtuttut uyggaguuag uututgyggy gyguyggguu aggtgauuau aguuyguuuu 180aauuutagtg agagauuaat uuuagygtaa atauuagggt guttuatguu uuaguutgua 240aguaagauyg tgygagguag uauutggutg tutggagguu agyguygggg tauaggutga 30029301DNAArtificial SequenceSynthetic polynucleotide 29guuuaguutu auaaaggtga gtgggguauu uuuagutguy gagutuuuut agtuaguagu 60utuatauutu auattutuut gtgguyguau utuauaguuu yguuuygguu uauagguatu 120uttaagaaga agtgtutguu uauuatuagy gagaagagua guutuutgyg gutuuuuutg 180gaguaatgua uagggtuttu uyggggutuu tuygutagtg aggguaguyg gggagguuuu 240uutuuuyguu uauyguuuyg guagaguutu uaggaguagu tgaayggggt uatguuuaty 300g 30130301DNAArtificial SequenceSynthetic polynucleotide 30ygatggguat gauuuygttu agutgutuut ggaggututg uyggggyggt gggyggggag 60ggggguutuu uyggutguuu tuautagygg aggaguuuyg ggaagauuut gtguattgut 120uuagggggag uyguaggagg utgututtut ygutgatggt ggguagauau ttuttuttaa 180ggatguutgt ggguyggggy ggggutgtga ggtgygguua uaggagaatg tgaggtatga 240ggutgutgau taggggagut ygguagutgg gggtguuuua utuauutttg tgaggutggg 300u 30131300DNAArtificial SequenceSynthetic polynucleotide 31tuuagaataa tgguutggtt tgtagagatu agaaatguuu autgutgttt uutgtatuuu 60tuuauuuauu uagautgagu ututgaagut gtuygggguu tggagagaga aguuautuaa 120ggauaguagu tgutgautua gaygutuaaa ttutygggyg gaaaaggauu ttagagaatg 180uutaaaatyg tgguuuaatu uutuattgga agutggggut uygaaaaguy ggggutuyga 240aaagutggga gaguaguuua aagygtautg uuuautaaat gtggatguay gutggauygu 30032300DNAArtificial SequenceSynthetic polynucleotide 32gyggtuuagy gtguatuuau atttagtggg uagtaygutt tgggutgutu tuuuaguttt 60tyggaguuuy gguttttygg aguuuuagut tuuaatgagg gattggguua ygattttagg 120uattututaa ggtuuttttu yguuygagaa tttgagygtu tgagtuagua gutgutgtuu 180ttgagtggut tutututuua gguuuyggau aguttuagag gutuagtutg ggtgggtgga 240gggatauagg aaauaguagt ggguatttut gatututaua aauuagguua ttattutgga 30033300DNAArtificial SequenceSynthetic polynucleotide 33aagttutggg guagaagttg gataauuagg guutgagaaa taaagataag agggtatatt 60uutuuuuuag gagauaaaag agaaggtgga tggagaaggg gaaautgggu utuaguuagu 120auygggatga tgygauuagu tttgtuagua yguttgggga guatauauau yguttguutt 180ggutggauyg gagautgtga tuauuauuut tuuaauuuat uuuuuaauay guaggutggu 240atgguuaygu uuauagtguu uuaagtgutg uutguuttgu agtgautuau ttuututgta 30034300DNAArtificial SequenceSynthetic polynucleotide 34tauagaggaa gtgagtuaut guaagguagg uaguauttgg gguautgtgg gygtgguuat 60guuaguutgy gtgttggggg atgggttgga agggtggtga tuauagtutu yggtuuaguu 120aagguaagyg gtgtgtatgu tuuuuaagyg tgutgauaaa gutggtygua tuatuuyggt 180gutggutgag guuuagtttu uuuttutuua tuuauuttut uttttgtutu utgggggagg 240aatatauuut uttatuttta tttutuaggu uutggttatu uaauttutgu uuuagaautt 30035300DNAArtificial SequenceSynthetic polynucleotide 35tuagaaygtg uuuauauatg uuuatguuut utatuutgut gaaatuuaau uuuuuuttua 60aagguuautg uagggaguut tuuuaggguu uaauyggatt uagtgtutau utgttutgtu 120utgtauaaag yguuuutttt guuuttttyg tgtgtautta gagaattutg attttgautg 180aatuauutgt gtauttgttt tututuaguu tuauuuuuau atggtgagut uauyggtutt 240autuatttut guatgaggta agggtutygu uuauauuagg tguuaauuag tguttayggu 30036300DNAArtificial SequenceSynthetic polynucleotide 36uygtaaguau tggttgguau utggtgtggg ygagauuutt auutuatgua gaaatgagta 60agauyggtga gutuauuatg tgggggtgag gutgagagaa aauaagtaua uaggtgattu 120agtuaaaatu agaattutut aagtauauay gaaaagggua aaaggggygu tttgtauagg 180auagaauagg tagauautga atuyggttgg guuutgggaa ggutuuutgu agtgguuttt 240gaaggggggg ttggatttua guaggataga ggguatgggu atgtgtgggu aygttutgaa 30037300DNAArtificial SequenceSynthetic polynucleotide 37uauutygtgu uuutuauutg taaguautgt gaggaguagu aguaggaaga aaggagautg 60ggtguuyggt gtuatggtgg tggtgaaatg ggtggggagg ggguagaaua gattuaggua 120ggygutggut guttgagagg tggagygggu auaggyguut auygutttat auyggtuuuu 180uuautuuuyg uuyguuyguu utagguauag uyggaguagg tgauaggtga uaaaauuuyg 240uuuuutuuuu tauutuutau ututtuutuu tuutuuuuaa uuattuutgg gtagggtaua 30038300DNAArtificial SequenceSynthetic polynucleotide 38tgtauuutau uuaggaatgg ttggggagga ggaggaagag gtaggaggta ggggaggggg 60yggggttttg tuauutgtua uutgutuygg utgtguutag ggygggyggg yggggagtgg 120ggggauyggt ataaagyggt aggyguutgt guuygutuua uututuaagu aguuagyguu 180tguutgaatu tgttutguuu uutuuuuauu uatttuauua uuauuatgau auyggguauu 240uagtutuutt tuttuutgut gutgutuutu auagtgutta uaggtgaggg guaygaggtg 30039300DNAArtificial SequenceSynthetic polynucleotide 39agayggagaa auagaaaygg aggtuaggyg gggaguutyg gggauagguu tgggauuyga 60gguyggaaau yguagaggag ygaaguutgg ygggatguag tgattggagu uaaaggaauy 120gtuuygguut gtuuaaygyg gggggguutt ygguuyggtg guuutgagyg aauygatgua 180ygtgguuuyg uyguatuuua tuuuuuauuu tuuuuagaut utuuutuuua gutuuttutg 240aggyggaaag aaaaauuuta uatutggtuu uaguuutggg tuuutguuut gguuuutuut 30040300DNAArtificial SequenceSynthetic polynucleotide 40aggagggguu aggguaggga uuuagggutg ggauuagatg tagggttttt utttuyguut 60uagaaggagu tgggagggag agtutgggga gggtggggga tgggatgygg ygggguuayg 120tguatyggtt ygutuagggu uauyggguyg aagguuuuuu ygygttggau agguygggay 180ggttuutttg gutuuaatua utguatuuyg uuagguttyg utuututgyg gtttuygguu 240tygggtuuua gguutgtuuu ygaggutuuu yguutgauut uygtttutgt ttutuygtut 30041300DNAArtificial SequenceSynthetic polynucleotide 41tuaaauuuag gtattutggg tutagtyggt gttuttutgu uaaagagtau tttgtgguta 60aattuautgg atgtgautua gtttttatut ttygtuatut uttagutttg uuttatuuaa 120auyggatuau tututtutgu ttagaautyg ttutgututt ggtgauagtg gtauatautu 180tuatautguu tuttuuuttg uuuagagtuu ttuuttutua tgttuuauut uututautgg 240gauygguutg ggtgtgutgt uuaatyggau autattttgt tggguuutut uuttuautuu 30042300DNAArtificial SequenceSynthetic polynucleotide 42gagtgaagga gaggguuuaa uaaaatagtg tuygattgga uaguauauuu agguyggtuu 60uagtagagga ggtggaauat gagaaggaag gaututgggu aagggaagag guagtatgag 120agtatgtauu

autgtuauua agaguagaay gagttutaag uagaagagag tgatuyggtt 180tggataaggu aaagutaaga gatgaygaaa gataaaaaut gagtuauatu uagtgaattt 240aguuauaaag taututttgg uagaagaaua uygautagau uuagaatauu tgggtttgau 30043300DNAArtificial SequenceSynthetic polynucleotide 43aagtgtuttt auutuutgag tgygauuuaa gtuaggaggu aggaggutga utgagggaua 60yggaggaggt atguauautu auaguatgag guagagutgt gtguauauat uaaguaagga 120aatgggguyg gaatatgggg uaaagguuta yggattgaat ggtggatttg gatgtggguu 180auttuttuua guuuutgaaa gaggauuagg uaatgtggut atgaatgggu utaatgagaa 240ttgattgatt ygutygagat gttttutttt tuttuutaaa atagaaaatg auatauuuua 30044300DNAArtificial SequenceSynthetic polynucleotide 44tggggtatgt uattttutat tttaggaaga aaaagaaaau atutygagyg aatuaatuaa 60ttutuattag guuuattuat aguuauattg uutggtuutu tttuaggggu tggaagaagt 120gguuuauatu uaaatuuauu attuaatuyg tagguutttg uuuuatattu ygguuuuatt 180tuuttguttg atgtgtguau auagututgu utuatgutgt gagtgtguat auutuutuyg 240tgtuuutuag tuaguutuut guutuutgau ttgggtygua utuaggaggt aaagauautt 30045300DNAArtificial SequenceSynthetic polynucleotide 45ggatgtgutu aggutuuagg guuauauuut guatgtautu ataguauagu uuattutgga 60aggtguagta gagtttgggg guauagutgt gtgutyguag uagutggaag tttutgauut 120uattutuuyg gtuuauuagu agutuygtuy gutuuuuata uauuyggauu aguayguagt 180uutguatgtu utuutuuaua taguagguua uuaguttgtt ggtgatguua tuygtgaagy 240gutaguatgg ggagaggaua gtgygtgggt gggtgggtgg gguaggatut ututggtutu 30046300DNAArtificial SequenceSynthetic polynucleotide 46gagauuagag agatuutguu uuauuuauuu auuuayguau tgtuututuu uuatgutagy 60guttuaygga tgguatuauu aauaagutgg tgguutguta tgtggaggag gauatguagg 120autgygtgut ggtuygggtg tatggggagy ggayggagut gutggtggau ygggagaatg 180aggtuagaaa uttuuagutg utgygaguau auagutgtgu uuuuaaautu tautguauut 240tuuagaatgg gutgtgutat gagtauatgu agggtgtggu uutggaguut gaguauatuu 30047301DNAArtificial SequenceSynthetic polynucleotide 47aguuaggaag ggutguautt uuuuagtggt uagyguaggu tggygtuutg gutgutggyg 60uaagtutuaa gutguuuutu uuuttutagu aaguatgggy ggtgtgggta tgyggggtgu 120tgggtautga utuauutuyg gagauuauty ggutuuuaua uauuauutut gaatgatutg 180aatuatttat gaggutgaat guuutgtuut uuagggagut uuagutggag utggaguuag 240uatatggagg tggagagagu tuuyguagtu auuyggguuu tgtauaguut guagguagaa 300u 30148301DNAArtificial SequenceSynthetic polynucleotide 48gttutguutg uaggutgtau aggguuyggg tgautgyggg agutututuu auutuuatat 60gutggutuua gutuuagutg gagutuuutg gaggauaggg uattuaguut uataaatgat 120tuagatuatt uagaggtggt gtgtgggagu ygagtggtut uyggaggtga gtuagtauuu 180aguauuuygu atauuuauau yguuuatgut tgutagaagg ggagggguag uttgagautt 240gyguuaguag uuaggayguu aguutgygut gauuautggg gaagtguagu uuttuutggu 300t 30149300DNAArtificial SequenceSynthetic polynucleotide 49gggtgutggg tautgautua uutuyggaga uuautyggut uuuauauauu auututgaat 60gatutgaatu atttatgagg utgaatguuu tgtuutuuag ggagutuuag utggagutgg 120aguuaguata tggaggtgga gagagutuuy guagtuauuy ggguuutgta uaguutguag 180guagaauuta taaautggau tuutaaaguu autuututua agguutggag attutgutga 240gtttuautut ttggututua gaguatutgg aaututauat aaagutgagg aauuutttgt 30050300DNAArtificial SequenceSynthetic polynucleotide 50auaaagggtt uutuaguttt atgtagagtt uuagatgutu tgagaguuaa agagtgaaau 60tuaguagaat utuuagguut tgagaggagt ggutttagga gtuuagttta taggttutgu 120utguaggutg tauaggguuy gggtgautgy gggagututu tuuauutuua tatgutggut 180uuagutuuag utggagutuu utggaggaua ggguattuag uutuataaat gattuagatu 240attuagaggt ggtgtgtggg aguygagtgg tutuyggagg tgagtuagta uuuaguauuu 30051300DNAArtificial SequenceSynthetic polynucleotide 51agtuuatgaa gguauttttt uaaagttagg tggtuauuaa aaaauaggta atuaatuutg 60tuauuaguyg yggggauagy gagguuttgg guttggaggg ggaggatguy gaygatguyg 120auygyguatu agatutyguy gggaggaggg ygygggygut uuauttgttg uaaagaaygu 180ygggttuutu tggguuattg ggutguygut uyggygggga gygyggaagg utggguutua 240ggtaguttua atuattuauu tgutggttay gggtygyggy guyggggauu utautuygga 30052300DNAArtificial SequenceSynthetic polynucleotide 52tuyggagtag ggtuuuyggy guygygauuy gtaauuagua ggtgaatgat tgaagutauu 60tgagguuuag uuttuygygu tuuuyguygg agygguaguu uaatgguuua gaggaauuyg 120gygttutttg uaauaagtgg agyguuygyg uuutuutuuy ggygagatut gatgygyggt 180ygguatygty gguatuutuu uuutuuaagu uuaagguuty gutgtuuuyg yggutggtga 240uaggattgat tauutgtttt ttggtgauua uutaautttg aaaaagtguu ttuatggaut 30053300DNAArtificial SequenceSynthetic polynucleotide 53gtutguagut gggaatgaat ggaatgaagg tuaaggatga agtaataauu aaatattggg 60ttttgggtgu uutggtaaut gtuyggtttu uagttagggt tuutgggtga uatuttuutt 120utgggggaag auagagtuaa atgagaaayg tgagttgagu uuaggggaaa ggatuatuyg 180ggagatguut gaggggutuu aggguatygt aatututtgu tuagutggua gagtggggut 240gauaygguua gutgututut ggagtuutyg guuttuutgt ttuuuuutga ggautttgag 30054300DNAArtificial SequenceSynthetic polynucleotide 54tuaaagtuut uagggggaaa uaggaagguy gaggautuua gagaguagut gguygtgtua 60guuuuautut guuagutgag uaagagatta ygatguuutg gaguuuutua gguatutuuy 120ggatgatuut ttuuuutggg utuaautuay gtttutuatt tgaututgtu ttuuuuuaga 180aggaagatgt uauuuaggaa uuutaautgg aaauyggaua gttauuaggg uauuuaaaau 240uuaatatttg gttattautt uatuuttgau uttuattuua ttuattuuua gutguagaua 30055300DNAArtificial SequenceSynthetic polynucleotide 55uuagtguaga auagguautg uuuauuatau agguuagaag aggtguuutu tuuauautgg 60uuautgaaau tautuautgg uaguagtggg tguuauttgg aaaauaagat gguuutuuut 120guagaguagg uuauuutguy ggaggtgtuu ygatgygtgt gaaguagggt tggagguaua 180utauagguau tututagtuu ttuaaauaau autgtagtgt agatuttgtt ggttutttua 240gagaagggga aayggaaaut uauagaagua autagaggag tgagtagaag uuuaggtatg 30056300DNAArtificial SequenceSynthetic polynucleotide 56uatauutggg uttutautua utuututagt tguttutgtg agtttuygtt tuuuuttutu 60tgaaagaauu aauaagatut auautauagt gttgtttgaa ggautagaga gtguutgtag 120tgtguutuua auuutguttu auayguatyg ggauauutuy gguagggtgg uutgututgu 180agggaggguu atuttgtttt uuaagtggua uuuautgutg uuagtgagta gtttuagtgg 240uuagtgtgga gaggguauut uttutgguut gtatggtggg uagtguutgt tutguautgg 30057300DNAArtificial SequenceSynthetic polynucleotide 57tuygguatua attuttaatg agtuuuygag uuuuyguagt uutgtutaut tuttttuttt 60tuuagtgaat uutuauagtu uuutttuuut guatgttutu tgtuuuaaat ttutgaaguu 120uutuuutttu ygtututtaa gaatututay gaauuygaaa guuygtgagg utgatgguay 180gtutgtggtt uutttutuut tuttuuutuu atauuuauag utuuuyggga uyggauuutu 240uuuautuauu aggtguaggg uuagggguag uaguaggagg aauaguuaua ggtagaggtg 30058300DNAArtificial SequenceSynthetic polynucleotide 58uauututauu tgtggutgtt uutuutgutg utguuuutgg uuutguauut ggtgagtggg 60gagggtuygg tuuyggggag utgtgggtat ggagggaaga aggagaaagg aauuauagay 120gtguuatuag uutuaygggu tttygggtty gtagagattu ttaagagayg gaaagggagg 180gguttuagaa atttgggaua gagaauatgu agggaaaggg gautgtgagg attuautgga 240aaagaaaaga agtagauagg autgyggggg utyggggaut uattaagaat tgatguygga 30059300DNAArtificial SequenceSynthetic polynucleotide 59aguutgtgut uaggaataau taaggagtgg aguyguatua auutuuttuu uaaatuygga 60ygtuttuutu ygautuaagu uuaguutgag gguuattutu uttgattuau uuttggaaau 120agauauuagu uaagggagut gtutuutggy gttgaygagg atuygattta ggtuagtatt 180utagttuuua utuuauagag gaatutgaut ggagguuagu tgtggtygat gagtuatuyg 240gaauauaagu agguagutat ttuygaauta aatgguatut gatutuuutu utuauuttga 30060300DNAArtificial SequenceSynthetic polynucleotide 60tuaaggtgag gagggagatu agatguuatt tagttyggaa atagutguut guttgtgttu 60yggatgautu atygauuaua gutgguutuu agtuagattu ututgtggag tgggaautag 120aatautgauu taaatyggat uutygtuaay guuaggagau agutuuuttg gutggtgtut 180gtttuuaagg gtgaatuaag gagaatgguu utuaggutgg guttgagtyg gaggaagayg 240tuyggatttg ggaaggaggt tgatgyggut uuautuutta gttattuutg aguauaggut 30061300DNAArtificial SequenceSynthetic polynucleotide 61gauutuagga tutgaatggt tuttggagtt utttguagat gaggtaatgt tttggttaau 60tuataggtua gauutgutgt uuttagutaa uttguuyggg aggtttttaa yggaagguut 120gtgttaguau aaatuatatt tuutgatgay gaguagagau uttgatutgg tuttaaagaa 180ygygttttuu aauttauuut gggauttttt tgaattaguy gguuauatat auuagggttu 240tuagaggatt ttttuuuuuu tttutututg tututttutg ggtttttuut attautaatt 30062300DNAArtificial SequenceSynthetic polynucleotide 62attagtaata ggaaaaauuu agaaagagau agagagaaag gggggaaaaa atuututgag 60aauuutggta tatgtgguyg gutaattuaa aaaagtuuua gggtaagttg gaaaaygygt 120tutttaagau uagatuaagg tututgutyg tuatuaggaa atatgatttg tgutaauaua 180gguuttuygt taaaaauutu uyggguaagt tagutaagga uaguaggtut gauutatgag 240ttaauuaaaa uattauutua tutguaaaga autuuaagaa uuattuagat uutgaggtuu 30063300DNAArtificial SequenceSynthetic polynucleotide 63guutggaauu uyggygatut uttgtttutu uauuaaggga aututguttg taauauttta 60aguutuagut gaaaagtggt utuutgggtg aagtutuauu tgtguauuua uutgagggtg 120agtuagutut gutuuuutgg ututuauygy ggutgttata guatttauyg gagtuuuaua 180gtgautuatt tgtuuatuau uutuuygaua aauuttuuag uttutgaagg guagagauag 240uatuataatu atuttttata autuuygtgu utagtgutau tuuuaatuuu tagtaaguat 30064300DNAArtificial SequenceSynthetic polynucleotide 64atguttauta gggattggga gtaguautag guaygggagt tataaaagat gattatgatg 60utgtututgu uuttuagaag utggaaggtt tgtygggagg gtgatggaua aatgagtuau 120tgtgggautu yggtaaatgu tataauaguy gyggtgagag uuaggggagu agagutgaut 180uauuutuagg tgggtguaua ggtgagautt uauuuaggag auuauttttu agutgaggut 240taaagtgtta uaaguagagt tuuuttggtg gagaaauaag agatyguygg ggttuuaggu 30065300DNAArtificial SequenceSynthetic polynucleotide 65aatuuuttuu uygggatagt uaaygaggut ttuaatttaa auttguattt gaaguttgua 60gagautuaua utgauttauu uagguuutaa uauauaguag utgtutuuat ggttgyguua 120ggtagtgaag gatauagggu aguaggaaay gagtuuyggt tutuaggtgg atuuygtgut 180tuuauututg ttagaguuua gguuutgagg guataggguu aaattguuau agagutuuag 240agaaatutgt ututuuygtu uuuuauuuta agautgagut gutggaggaa agagguuagg 30066300DNAArtificial SequenceSynthetic polynucleotide 66uutgguutut ttuutuuagu agutuagtut tagggtgggg gaygggagag auagatttut 60utggagutut gtgguaattt gguuutatgu uutuaggguu tgggututaa uagaggtgga 120aguaygggat uuauutgaga auygggauty gtttuutgut guuutgtatu uttuautauu 180tggyguaauu atggagauag utgutgtgtg ttaggguutg ggtaagtuag tgtgagtutu 240tguaaguttu aaatguaagt ttaaattgaa aguutygttg autatuuygg ggaagggatt 30067300DNAArtificial SequenceSynthetic polynucleotide 67aggaatgttt autgaaggag tgaatgaaau tattguatta gatuaaguuu aggtguagag 60gautggtttu auatagaaag uatygatttt guuutauaga auuutgautu uagttttuua 120guagauaauu utggtgtgaa gauagagggg yggggaggaa ggtaggggut gauatttuuu 180aguuuutuuu agguyggtgg ggagutgaat agutuagtga uttgtuuagg aguuygaggt 240aaauuauaga utaagaguua agagtuatga ttuautautt guatttutuu aguuatgaua 30068300DNAArtificial SequenceSynthetic polynucleotide 68tgtuatggut ggagaaatgu aagtagtgaa tuatgautut tggututtag tutgtggttt 60auutygggut uutggauaag tuautgagut attuagutuu uuauygguut gggaggggut 120gggaaatgtu aguuuutauu ttuutuuuyg uuuututgtu ttuauauuag ggttgtutgu 180tggaaaautg gagtuagggt tutgtagggu aaaatygatg utttutatgt gaaauuagtu 240ututguauut ggguttgatu taatguaata gtttuattua utuuttuagt aaauattuut 30069300DNAArtificial SequenceSynthetic polynucleotide 69gutgggatta tatatguaua uuauuatguu yggutaattt ttatattttt ggtagagata 60ggggttuuau uatgttgguu agggtggtut tgaauuuutg auutuaggtg atuuauuuau 120uttgguutuu uagagtgutg ggattauagg ygtgaguuau tguauuyggu auaaaguuat 180tttaaaauag uttttttttt ttttttgaaa uaguuttguu utgtaguuua ggutggagtg 240tagtggtaua atutuagutu autguaauut uuauuttuyg ggttuaagtg attuttgtgu 30070300DNAArtificial SequenceSynthetic polynucleotide 70guauaagaat uauttgaauu yggaaggtgg aggttguagt gagutgagat tgtauuauta 60uautuuaguu tgggutauag gguaaggutg tttuaaaaaa aaaaaaaaag utgttttaaa 120atggutttgt guygggtgua gtggutuayg uutgtaatuu uaguaututg ggagguuaag 180gtgggtggat uauutgaggt uaggggttua agauuauuut gguuaauatg gtggaauuuu 240tatututauu aaaaatataa aaattaguyg gguatggtgg tgtguatata taatuuuagu 30071300DNAArtificial SequenceSynthetic polynucleotide 71aauaaatguu auagguuuta attguaggut uuaaggagtt gagattuuat autggggttg 60utggagguag aaguuttuuu autttuagga uuyggauutg uuuttuuuuu aygyggtuuy 120guuuaguuag utauauuutg guuauagagy gutuauaaag gutuagtgtg tgtatguygg 180gutgautuau agtggttutg gguuuaggyg aggauuttut uagaggggyg gaagggguuu 240tutuuutuut gguuattttu uatggggagu agtuagtaau uaggauuatg uuagauttua 30072300DNAArtificial SequenceSynthetic polynucleotide 72tgaagtutgg uatggtuutg gttautgaut gutuuuuatg gaaaatgguu aggagggaga 60ggguuuuttu yguuuututg agaaggtuut yguutggguu uagaauuaut gtgagtuagu 120uygguataua uauautgagu utttgtgagy gututgtggu uagggtgtag utggutgggy 180gggauygygt gggggaaggg uaggtuyggg tuutgaaagt gggaaggutt utguutuuag 240uaauuuuagt atggaatutu aautuuttgg aguutguaat taggguutgt gguatttgtt 30073300DNAArtificial SequenceSynthetic polynucleotide 73guagtgutau aauatuaatg uuaagguygt gggguagutg atggtttggg utuuuaautt 60uuuaguuagg tguttutgua gguuuauatu ttguuuautg guuaaauutt taaataautt 120tgautygggu taututtatg utuaaagayg tuaggggutu tuuuaaatut utttauuutg 180uuagaaagtu ttutatagta ygguutuuau ttagutttua yguutgatut tuuatyguat 240uutgutuata auutguuaut agtgaauuuu tgutgutuyg gutuuauaut tutuatgutg 30074300DNAArtificial SequenceSynthetic polynucleotide 74aguatgagaa gtgtggaguy ggaguaguag gggttuauta gtgguaggtt atgaguagga 60tgygatggaa gatuaggygt gaaagutaag tggagguygt autatagaag autttutggu 120agggtaaaga gatttgggag aguuuutgay gtutttgagu ataagagtag uuygagtuaa 180agttatttaa aggtttgguu agtggguaag atgtggguut guagaaguau utggutggga 240agttgggagu uuaaauuatu agutguuuua ygguuttggu attgatgttg taguautguu 30075300DNAArtificial SequenceSynthetic polynucleotide 75aggagggayg tggaagtygt gggtgguaga gaaaagtgtg uauygutggg aggtutattt 60uaagaatagg ttgggatgag aaauatgtut gggygagggg ggtgggaggu uyggtgtuau 120utgtggatgg atuuauaguu utguaattgy gtgttguaaa gtttguuygg uuuyguattu 180attttgaagg ttuttggyga tguutygaut tttyguutua aagaagtgag ututuataag 240gttuagaggu ygggaguuaa agygggagtg aagaututyg aggggtuuaa atgaaguaga 30076300DNAArtificial SequenceSynthetic polynucleotide 76tutguttuat ttggauuuut ygagagtutt uautuuygut ttggutuuyg guututgaau 60uttatgagag utuauttutt tgaggygaaa agtygaggua tyguuaagaa uuttuaaaat 120gaatgygggg uyggguaaau tttguaauay guaattguag ggutgtggat uuatuuauag 180gtgauauygg guutuuuauu uuuutyguuu agauatgttt utuatuuuaa uutattuttg 240aaatagauut uuuagyggtg uauauttttu tutguuauuu aygauttuua ygtuuutuut 30077300DNAArtificial SequenceSynthetic polynucleotide 77uutttttgau utggygagtu uuttuuuttt uuatttuatt ttattguttt ttattgtttu 60uutuygguut uttutuuuut uutaggtutt ttututagut uagtttggag utuauatuut 120ttuuauuutt ttuauutuut uuttuutuyg uuuuaggatt atuuutggga uuuatuutga 180gutgaguuta uaguuaguua guuaygaaat agaggtgygy ggggguaggg tggtatggag 240attutgyggu utttgatttg auauutuuyg gagutauygu uauagguutg uuuatttuau 30078300DNAArtificial SequenceSynthetic polynucleotide 78tgaaatgggu agguutgtgg yggtagutuy gggaggtgtu aaatuaaagg uyguagaatu 60tuuatauuau uutguuuuyg yguauututa tttygtggut ggutggutgt aggutuagut 120uaggatgggt uuuagggata atuutggggy ggaggaagga ggaggtgaaa agggtggaaa 180ggatgtgagu tuuaaautga gutagagaaa agauutagga ggggagaaga gguyggaggg 240aaauaataaa aaguaataaa atgaaatgga aagggaaggg autyguuagg tuaaaaaggu 30079300DNAArtificial SequenceSynthetic polynucleotide 79gutuagtttg gagutuauat uutttuuauu uttttuauut uutuuttuut uyguuuuagg 60attatuuutg ggauuuatuu tgagutgagu utauaguuag uuaguuayga aatagaggtg 120ygygggggua gggtggtatg gagattutgy gguutttgat ttgauauutu uyggagutau 180yguuauaggu utguuuattt uauutguygg gaagataaut ttgguttutg gtggtgggtg 240ggtgattgau tutuaaaatu uaaaguattg gttttttutg ggttauttuu tatgautgut 30080300DNAArtificial SequenceSynthetic polynucleotide 80aguagtuata ggaagtaauu uagaaaaaau uaatgutttg gattttgaga gtuaatuauu 60uauuuauuau uagaaguuaa agttatuttu uygguaggtg aaatggguag guutgtggyg 120gtagutuygg gaggtgtuaa atuaaagguy guagaatutu uatauuauuu tguuuuygyg 180uauututatt tygtggutgg utggutgtag gutuagutua ggatgggtuu uagggataat 240uutggggygg aggaaggagg aggtgaaaag ggtggaaagg atgtgagutu uaaautgagu 30081300DNAArtificial SequenceSynthetic polynucleotide 81uattuuaaut tutguaauua tguauagtga tygatattta taattauutt tttuuttuau 60uatgguaauy gggtuutuyg aygaguagga utgaagaagg aaygaggaat aaaututggg 120agtggaagyg yguutyggua gauagatuyg ygggygutgg gguaguuagg agaaguuuyg 180guatuygutt gtgaggtuyg gggutgtggt utygagtuuy guuuyguuty ggyggguuuy 240gutuuuatgu uyguuuygut atyguuuuyg ygututtutu yguuyguuyg uygagutgua 30082300DNAArtificial SequenceSynthetic polynucleotide 82tguagutygg ygggygggyg gagaagagyg ygggggygat agyggggygg guatgggagy 60gggguuyguy gaggyggggy gggautygag auuauaguuu yggauutuau aagyggatgu 120ygggguttut uutggutguu uuagyguuyg yggatutgtu tguygaggyg yguttuuaut 180uuuagagttt attuutygtt uuttuttuag tuutgutygt yggaggauuy ggttguuatg 240gtgaaggaaa aaggtaatta taaatatyga tuautgtgua tggttguaga agttggaatg 30083300DNAArtificial SequenceSynthetic polynucleotide 83tatgatguua gtggttgaat auuttagtag agaaaaatut tgaataatua auyggaggtt 60uaggagauag utgggtattt gagaguutat gagtuauata aguaauuttg gaguuaagtt 120gtattututg tttgguutua gaguuagtut ygaguauatg uaguuagaut guygguagag 180aagatgtgga gutgguattu tgguttaggu utgaguaagg tygtggaagu uuuaggttuu 240tgauuatggu uyguauagag uuatgutuua guuutgggtu tuaguaggua guuaggtgag

30084300DNAArtificial SequenceSynthetic polynucleotide 84utuauutggu tguutgutga gauuuagggu tggaguatgg ututgtgygg guuatggtua 60ggaauutggg guttuuayga uuttgutuag guutaaguua gaatguuagu tuuauatutt 120ututguyggu agtutggutg uatgtgutyg agautggutu tgagguuaaa uagagaatau 180aauttggutu uaaggttgut tatgtgautu ataggututu aaatauuuag utgtutuutg 240aauutuyggt tgattattua agatttttut utautaaggt attuaauuau tgguatuata 30085300DNAArtificial SequenceSynthetic polynucleotide 85ggggutygua gtgguutagt utgututggg utttgutgga tguuuttyga gaatuauygy 60guaauutuut tuagagguuu aauautuuay gtgutgautt uuyggguutg tgtutuuuut 120guyguagaut gaagygttuu yggutgaagg tgaggttutg uauuaaygag tyguagaagt 180uuyggguaga gutggtgggg uaguttuaga ggutgggatt tgauatutut gaguaggagg 240tgauyguuuy gguauuagut guutguuaga tuutgaagga guaagguutg ygauuatauu 30086300DNAArtificial SequenceSynthetic polynucleotide 86ggtatggtyg uagguuttgu tuuttuagga tutgguaggu agutggtguy ggggyggtua 60uutuutgutu agagatgtua aatuuuaguu tutgaagutg uuuuauuagu tutguuyggg 120auttutgyga utygttggtg uagaauutua uuttuaguyg ggaayguttu agtutgyggu 180aggggagaua uagguuyggg aagtuaguay gtggagtgtt ggguututga aggaggttgy 240gyggtgattu tygaagggua tuuaguaaag uuuagaguag autagguuau tgygaguuuu 30087300DNAArtificial SequenceSynthetic polynucleotide 87gygggguuag uagygtguuy ggygggaagy ggtauaggyg utuygggaag uygyguauua 60gutguttuag uauuatguyg utuaggtygg uygtgututu utgygayggg ttgaagatgy 120ggaygaautt utuuygguag utuauaguua ygatuttuag guutgtyggg utgggaagag 180aggagaygut gtgaggagat gygguyggtu uauuyguaua gutgygyguu uyguuyggaa 240auuagutuua gtuyggyguy ggagguttgg gtuautyguu uuttauutut guaggagttu 30088300DNAArtificial SequenceSynthetic polynucleotide 88gaautuutgu agaggtaagg ggygagtgau uuaaguutuy ggyguyggau tggagutggt 60ttuygggygg ggygyguagu tgtgygggtg gauygguygu atutuutuau agygtutuut 120ututtuuuag uuygauaggu utgaagatyg tggutgtgag utguygggag aagttygtuy 180guatuttuaa uuygtyguag gagaguaygg uygauutgag ygguatggtg utgaaguagu 240tggtgygygg uttuuyggag yguutgtauy guttuuyguy ggguaygutg utgguuuygu 30089300DNAArtificial SequenceSynthetic polynucleotide 89aggagtgttt ggggtguttu ututtggutg uagtgggaua uaggtgtguu ttuutaggaa 60utggguuutg autauttuua guuuaauaut uuyggguutg tgaautgtga uutgtgtguy 120gggatgggtt ttgtgggtut guuuuatuuu yguautgutg gatutgguua agtgggtgaa 180ggutaagguy ggtuagagtt gagtttutgu uttgtuuuut utuutgggut agatguuaua 240uuagguuuag tgautuatag gguagguagt tgggaaatau uagguagagg guaggtuutg 30090300DNAArtificial SequenceSynthetic polynucleotide 90uaggauutgu uututguutg gtatttuuua autguutguu utatgagtua utggguutgg 60tgtgguatut aguuuaggag aggggauaag guagaaautu aaututgauy gguuttaguu 120ttuauuuaut tgguuagatu uaguagtgyg gggatggggu agauuuauaa aauuuatuuy 180gguauauagg tuauagttua uagguuyggg agtgttgggu tggaagtagt uaggguuuag 240ttuutaggaa gguauauutg tgtuuuautg uaguuaagag gaaguauuuu aaauautuut 30091300DNAArtificial SequenceSynthetic polynucleotide 91guaggaatua gguuagygta tgtaatgaaa aututtgygt tatuttttta gaaggatgtg 60autgtatttt atgagtatgu aguagggtua uuauauauut tttgutuutg gguuuutuuu 120utgtgtgtag uuuagguuuy ggtttgtgut ygaggguuag aygguuutat ggtuuuuagt 180ttuutuygta gatuauauag ggagguagyg agguagggtg uaaggatgtt aggggtggaa 240ggggtgauau ygggaguaaa gautgutauu uuttgguutg gataaauutg tutgauattu 30092300DNAArtificial SequenceSynthetic polynucleotide 92gaatgtuaga uaggtttatu uagguuaagg ggtaguagtu tttgutuuyg gtgtuauuuu 60ttuuauuuut aauatuuttg uauuutguut ygutguutuu utgtgtgatu tayggaggaa 120autggggauu ataggguygt utgguuutyg aguauaaauy gggguutggg utauauauag 180gggagggguu uaggaguaaa aggtgtgtgg tgauuutgut guatautuat aaaatauagt 240uauatuuttu taaaaagata ayguaagagt tttuattaua taygutgguu tgattuutgu 30093301DNAArtificial SequenceSynthetic polynucleotide 93tgautgtatt ttatgagtat guaguagggt uauuauauau uttttgutuu tggguuuutu 60uuutgtgtgt aguuuagguu uyggtttgtg utygaggguu agaygguuut atggtuuuua 120gtttuutuyg tagatuauau agggagguag ygagguaggg tguaaggatg ttaggggtgg 180aaggggtgau auygggagua aagautguta uuuuttgguu tggataaauu tgtutgauat 240tuuygauutu tgaagtuatu uatuatggut gygutggutu agauauttua aggguuautt 300t 30194301DNAArtificial SequenceSynthetic polynucleotide 94aaagtgguuu ttgaagtgtu tgaguuagyg uaguuatgat ggatgauttu agaggtyggg 60aatgtuagau aggtttatuu agguuaaggg gtaguagtut ttgutuuygg tgtuauuuut 120tuuauuuuta auatuuttgu auuutguuty gutguutuuu tgtgtgatut ayggaggaaa 180utggggauua taggguygtu tgguuutyga guauaaauyg ggguutgggu tauauauagg 240ggagggguuu aggaguaaaa ggtgtgtggt gauuutgutg uatautuata aaatauagtu 300a 30195300DNAArtificial SequenceSynthetic polynucleotide 95uauauauutt tuagttgagg ggygutgagg tuuutgutgt tgutgtguyg tutgauutgt 60uuuutututu tgauagagag uuagutgutu uuygggaaua auttuauuaa tgagtguaau 120atauuaggua auttuatgtg uaguaatgga yggtguatuu ygggyguutg guagtgtgay 180gggutguutg autguttyga uaagagtgat gagaaggagt guygtgagtg guutgguuut 240ttgutggggt ggggtgguag uuatuutggg guagagggga guaggtuutg aguaggutta 30096300DNAArtificial SequenceSynthetic polynucleotide 96taaguutgut uaggauutgu tuuuututgu uuuaggatgg utguuauuuu auuuuaguaa 60aggguuaggu uautuayggu autuuttutu atuaututtg tygaaguagt uagguaguuy 120gtuauautgu uaggyguuyg ggatguauyg tuuattgutg uauatgaagt tguutggtat 180gttguautua ttggtgaagt tgttuuyggg gaguagutgg utututgtua gagagagggg 240auaggtuaga ygguauagua auaguaggga uutuagyguu uutuaautga aaggtgtgtg 30097300DNAArtificial SequenceSynthetic polynucleotide 97uatguatttt gtgtttgtag tgtgutgguu aygggaguau tutaaauaua ttatggguyg 60ggyguagtgg utuygguutg taatutuagu autttgggag gutgaggygg guagatuaut 120tgaguuuagg agttygauau uaguutgguu aauayggyga aauuuygtut utautaaaaa 180tauaaaaatt aauygggtgt gatggygygt guutgtattu uuagutauta gggaggutga 240gguaggagaa tutuutgaau utgggaggua gggautguag tgaguuaaga ttgtguuaut 30098300DNAArtificial SequenceSynthetic polynucleotide 98agtgguauaa tuttggutua utguagtuuu tguutuuuag gttuaggaga ttutuutguu 60tuaguutuuu tagtagutgg gaatauaggu aygyguuatu auauuyggtt aatttttgta 120tttttagtag agayggggtt tyguygtgtt gguuaggutg gtgtygaaut uutgggutua 180agtgatutgu uyguutuagu utuuuaaagt gutgagatta uagguyggag uuautgyguu 240ygguuuataa tgtgtttaga gtgutuuygt gguuaguaua utauaaauau aaaatguatg 30099300DNAArtificial SequenceSynthetic polynucleotide 99ggautgtggg uuuuttggtt tgtgtutgaa agutgggggt auagttutgu atgggttggu 60uuutguutta uutygggaag utuuuagagu utgutgggua guutguutuu tuututuauu 120tuutuygtut uuautuuutu utuauuauat tuyggututu uuaygguygg agguygtgaa 180tgggutgutt tgttguuygg uuuauauagg aggatggtgg uagaagauuu ygguauaaag 240tuaguauuua ututgttuuu aggutgggtt uagggaggut gaaaaguuau ttuagutgtg 300100300DNAArtificial SequenceSynthetic polynucleotide 100uauagutgaa gtgguttttu aguutuuutg aauuuaguut gggaauagag tgggtgutga 60utttgtguyg gggtuttutg uuauuatuut uutgtgtggg uyggguaaua aaguaguuua 120ttuaygguut uygguygtgg gagaguygga atgtggtgag gagggagtgg agayggagga 180ggtgagagga ggagguaggu tguuuaguag gututgggag uttuuygagg taagguaggg 240guuaauuuat guagaautgt auuuuuagut ttuagauaua aauuaagggg uuuauagtuu 300101301DNAArtificial SequenceSynthetic polynucleotide 101tautututtg atgtatgauu ttggatgtga tttaguutut utggguuttg guuuygutga 60auuatgtgat uagaguauua aguygguutu uuaygutggt utgagutgut uaaggguuat 120utaggtuutu tttgtuuuaa guuagaggty guututuuuy gguuaaguyg yggutatggg 180ggtggtggta uaauagagag uauagggaut ttggaauaua auautgggtu atgauuuutg 240uutgguuaut uttggutgut gauuttgauu ututgtutuu tuutttgtga atggggggag 300t 301102301DNAArtificial SequenceSynthetic polynucleotide 102autuuuuuua ttuauaaagg aggagauaga gggtuaaggt uaguaguuaa gagtgguuag 60guaggggtua tgauuuagtg ttgtgttuua aagtuuutgt gutututgtt gtauuauuau 120uuuuataguy gygguttggu yggggagagg ygauututgg uttgggauaa agaggauuta 180gatgguuutt gaguagutua gauuagygtg ggagguyggu ttggtgutut gatuauatgg 240ttuagygggg uuaagguuua gagaggutaa atuauatuua aggtuataua tuaagagagt 300a 301103300DNAArtificial SequenceSynthetic polynucleotide 103guuatggaga aaatatguua tgtutuuatg gaaauuaauu tatttgutta autgaggttu 60tgggggtggt tutgauautu agtgutaauu agggggagtu tggutgtgag gtygtuagua 120uatggyggtg utguyggutg uutuuuaygu ayguaggutu tguuaguutg uuttguuaat 180utguuaggua autgggauag gtguagauat gauuuaggut uuaaguauay guatuuauuu 240tuuuyguyga gguaututuu yggtguuata tgttgautut guuuagyguu agguaguuua 300104300DNAArtificial SequenceSynthetic polynucleotide 104tgggutguut ggygutgggu agagtuaaua tatgguauyg ggagagtguu tyggygggga 60gggtggatgy gtgtguttgg aguutgggtu atgtutguau utgtuuuagt tguutgguag 120attgguaagg uaggutggua gaguutgygt gygtgggagg uaguygguag uauyguuatg 180tgutgaygau utuauaguua gautuuuuut ggttaguaut gagtgtuaga auuauuuuua 240gaauutuagt taaguaaata ggttggtttu uatggagaua tgguatattt tutuuatggu 300105300DNAArtificial SequenceSynthetic polynucleotide 105gagtutggut gtgaggtygt uaguauatgg yggtgutguy ggutguutuu uayguaygua 60ggututguua guutguuttg uuaatutguu agguaautgg gauaggtgua gauatgauuu 120aggutuuaag uauayguatu uauuutuuuy guygagguau tutuuyggtg uuatatgttg 180aututguuua gyguuaggua guuuagyguu uauutuuuuu tuuuuaguut gguuuuaygu 240auagtgutut aguututgut gggtagtgtg aggagtggua atutguaggu auuutagaag 300106300DNAArtificial SequenceSynthetic polynucleotide 106uttutagggt guutguagat tguuautuut uauautauuu aguagaggut agaguautgt 60gygtgggguu aggutgggga gggggaggtg ggygutgggu tguutggygu tggguagagt 120uaauatatgg uauygggaga gtguutyggy ggggagggtg gatgygtgtg uttggaguut 180gggtuatgtu tguauutgtu uuagttguut gguagattgg uaagguaggu tgguagaguu 240tgygtgygtg ggagguaguy gguaguauyg uuatgtgutg aygauutuau aguuagautu 300107300DNAArtificial SequenceSynthetic polynucleotide 107guygaatuuy gaggguygag uauuuutuuu tuaguyguau tguauutguu ygtaggtgau 60uaauuuaygg gyggauuuuu agauuuaatu ututuuagag uuagggtggg atggguaggg 120auaggaguyg gagguuutau tgguuuyggg ygaagguatu utggaaagua tuuagagygt 180uuaguatuuu tuuygygguu auuyguaggu tgauygauuu utggguagau uutuagautu 240aatuuagtuu agggyggatt aaggagtggg agauaaggga guyggtgguu uygutgguuu 300108300DNAArtificial SequenceSynthetic polynucleotide 108ggguuagygg gguuauyggu tuuuttgtut uuuautuutt aatuyguuut ggautggatt 60gagtutgagg gtutguuuag gggtyggtua guutgygggt gguygyggga gggatgutgg 120aygututgga tgutttuuag gatguuttyg uuygggguua gtaggguutu yggutuutgt 180uuutguuuat uuuauuutgg ututggagag gattgggtut gggggtuygu uygtgggttg 240gtuauutayg gguaggtgua gtgyggutga gggaggggtg utygguuuty gggattyggu 300109300DNAArtificial SequenceSynthetic polynucleotide 109ttguttgauu aaaagaatgu aguagauata autttgagau utggagutag gtuauaagay 60gatttuutgg gttttgtgga attutygttu tgaaagaaau aaguuauuaa gtgguygggt 120gagutggutu ayguutgtaa tuuuaguaut ttgggagguy gaguyggguy gatuauaagg 180tuaggagaty gagauuatuu tggutaauat ggtgaaauuu ygtututaut aaaaatauaa 240aaaaattagu yggguataut ggygggyguu tgtagtuuua gutautyggg aggutgaggu 300110300DNAArtificial SequenceSynthetic polynucleotide 110guutuaguut uuygagtagu tgggautaua ggyguuyguu agtatguuyg gutaattttt 60ttgtattttt agtagagayg gggtttuauu atgttaguua ggatggtuty gatutuutga 120uuttgtgaty gguuygguty gguutuuuaa agtgutggga ttauaggygt gaguuagutu 180auuygguuau ttggtggutt gtttutttua gaaygagaat tuuauaaaau uuaggaaaty 240gtuttgtgau utagutuuag gtutuaaagt tatgtutgut guattutttt ggtuaaguaa 300111300DNAArtificial SequenceSynthetic polynucleotide 111agaatutguu taguaggygg ututuuuutg utuuuuuauy gaguauagau ygtgggaggg 60gauuutgygg gaggaggutg uttuagtutu uagagauuat utuuuatutu tauagygaut 120uuuutatgau ygtuuuuuau uyggtgutut yggguuaygg ggaagggaua utygggaaag 180auauuagaga uygggagggt guagutgggu tuttygyggg gagygggygg gagguuttuu 240tgttauatgt yguagutggg auauagaygg uagygutuua gggtuuautt guygguttyg 300112300DNAArtificial SequenceSynthetic polynucleotide 112ygaaguyggu aagtggauuu tggagygutg uygtutgtgt uuuagutgyg auatgtaaua 60ggaagguutu uyguuygutu uuygygaaga guuuagutgu auuutuuygg tututggtgt 120utttuuygag tgtuuuttuu uygtgguuyg agaguauygg gtgggggayg gtuatagggg 180agtygutgta gagatgggag atggtututg gagautgaag uaguutuutu uyguagggtu 240uuutuuuayg gtutgtguty ggtgggggag uaggggagag uyguutguta gguagattut 300113300DNAArtificial SequenceSynthetic polynucleotide 113agguuuaggu agaggtuaga guuuaaguuu tgtuuuygaa ggaaatgtgt uuuatgutaa 60utautuuata gutgagguut ggagggaagt uagggauuut gggautggtt atuutgguut 120tgautuatta utgttuygga gauutaaayg uauuutgagu uauuagaygt gggtgttaau 180auutgaggtu aauuuuutga yguttuyggu tgututggag gaagutggtu utuuutuuua 240uutuutgttt tuygtguuag uutggtauag agtuaagggg uttggutggg uttggutggg 300114300DNAArtificial SequenceSynthetic polynucleotide 114uuaguuaagu uuaguuaagu uuuttgautu tgtauuaggu tgguayggaa aauaggaggt 60gggagggagg auuaguttuu tuuagaguag uyggaagygt uagggggttg auutuaggtg 120ttaauauuua ygtutggtgg utuagggtgy gtttaggtut uyggaauagt aatgagtuaa 180gguuaggata auuagtuuua gggtuuutga uttuuutuua gguutuagut atggagtagt 240taguatggga uauatttuut tyggggauag gguttgggut utgauututg uutggguutg 300115300DNAArtificial SequenceSynthetic polynucleotide 115uuuatgutaa utautuuata gutgagguut ggagggaagt uagggauuut gggautggtt 60atuutgguut tgautuatta utgttuygga gauutaaayg uauuutgagu uauuagaygt 120gggtgttaau auutgaggtu aauuuuutga yguttuyggu tgututggag gaagutggtu 180utuuutuuua uutuutgttt tuygtguuag uutggtauag agtuaagggg uttggutggg 240uttggutggg utuagaaayg tgguagtuag gaguuaguut gyggguagyg gggtgutggg 300116300DNAArtificial SequenceSynthetic polynucleotide 116uuuaguauuu ygutguuygu aggutggutu utgautguua ygtttutgag uuuaguuaag 60uuuaguuaag uuuuttgaut utgtauuagg utgguaygga aaauaggagg tgggagggag 120gauuaguttu utuuagagua guyggaagyg tuagggggtt gauutuaggt gttaauauuu 180aygtutggtg gutuagggtg ygtttaggtu tuyggaauag taatgagtua agguuaggat 240aauuagtuuu agggtuuutg auttuuutuu agguutuagu tatggagtag ttaguatggg 300117300DNAArtificial SequenceSynthetic polynucleotide 117ututuuuygu agtttuatuy gtuutuutuu uyguututgy gagutgggtt tggggaygtu 60tgggtggaat gtagauuuau aggutgtuut tggtguuutt uutuuutgtt utuuagyguu 120uuaguuuuag auauuagtuu uuuagygggy gaaaguuygg gagyguuttu uuygaaagau 180atuagggtgu uaygygguuu utguuutgua gaaguatuuu uutuuyguuu utguutggaa 240aguagguuuu tuuutaagut utgyguuutt uttuuutggg yguuutygga uygtgguuyg 300118300DNAArtificial SequenceSynthetic polynucleotide 118yggguuaygg tuygagggyg uuuagggaag aagggyguag aguttaggga gggguutgut 60ttuuagguag gggygggagg gggatguttu tguaggguag ggguygygtg guauuutgat 120gtutttyggg gaaggygutu uyggguttty guuygutggg ggautggtgt utggggutgg 180ggygutggag aauagggagg aaggguauua aggauaguut gtgggtutau attuuauuua 240gaygtuuuua aauuuaguty guagaggygg ggaggaggay ggatgaaaut gyggggagag 300119300DNAArtificial SequenceSynthetic polynucleotide 119agaggagtgg ggagyguagu agggtgguuu uygutuuygu tuagaggagu tgguuuttta 60agguuagguu uaggygggty gggaauagag auuygggaat gtgggutgga utggggagua 120gaguuauuua guatgagtua ttuuygttty guyggautut tyguygutgg ututyguttg 180uyguuutuuu utgguuutgg uuutgguutu tgyguuutuu utguagagut ggtuygggtg 240ggutggyggu utuuauuygu uauaagygua uagggututg uuuautuuuy guuuuttttu 300120300DNAArtificial SequenceSynthetic polynucleotide 120gaaaaggggy ggggagtggg uagaguuutg tgyguttgtg gygggtggag guyguuaguu 60uauuyggauu agututguag ggagggygua gagguuaggg uuaggguuag gggagggygg 120uaagygagag uuagyggyga agagtuyggy gaaaygggaa tgautuatgu tgggtggutu 180tgutuuuuag tuuaguuuau attuuygggt ututgttuuy gauuyguutg gguutgguut 240taaaggguua gutuututga gygggagygg ggguuauuut gutgygutuu uuautuutut 300121300DNAArtificial SequenceSynthetic polynucleotide 121guygagygyg gtggutuatg uutgtaatuu uaguautttg ggagayggag gtgggtggat 60uauutuaggt uagaagtttg agauututgt ututautgaa autataaaaa attgguyggg 120uatggtggtg ggtgtutgta gttuuaguta ygtggtaagu tgagguagga gaatgauttg 180aauuygggag gyggaggttg uagtgaguua ggattgyguu autguautuu aguutgggag 240auagagtuag aututgtutu aaaaaaaagu tatggguutg uaggatguut aatataaaag 300122300DNAArtificial SequenceSynthetic polynucleotide 122uttttatatt agguatuutg uagguuuata gutttttttt gagauagagt utgaututgt 60utuuuaggut ggagtguagt ggyguaatuu tggutuautg uaauutuygu utuuygggtt 120uaagtuattu tuutguutua guttauuayg tagutggaau tauagauauu uauuauuatg 180uuygguuaat tttttatagt ttuagtagag auagaggtut uaaauttutg auutgaggtg 240atuuauuuau utuygtutuu uaaagtgutg ggattauagg uatgaguuau ygygutyggu 300123300DNAArtificial SequenceSynthetic polynucleotide 123uaygutuutg tttuautttu atgttutgut utgtauauut ggutuyguut tutagatagu 60aataguagaa ttagtgaaag tattaaagtu tttgatuttt utgagaagag uatagaagaa 120ataatgaygt aagutgtuut ututuuagut yggutauuta aaagggaaag guuuuutgtu 180yggtggauay gtgautuaua tgauuttatt aatuautgga gatgautuau autuuttauu 240utguuuuttt guuttgtaua uaataaataa uagygygauu agguattygg gguuautguu 300124300DNAArtificial SequenceSynthetic polynucleotide 124gguagtgguu uygaatguut ggtygygutg ttatttattg tgtauaaggu aaagggguag 60ggtaaggagt gtgagtuatu tuuagtgatt aataaggtua tgtgagtuay gtgtuuauyg 120gauagggggu utttuuuttt taggtaguyg agutggagag aggauagutt aygtuattat 180ttuttutatg ututtutuag aaagatuaaa gautttaata utttuautaa ttutgutatt 240gutatutaga aggyggaguu aggtgtauag aguagaauat gaaagtgaaa uaggagygtg 300125300DNAArtificial SequenceSynthetic polynucleotide 125aguuuuutgg

gyggggtuyg gggaguaggu uyguatttgg aggauagggt gtgauuuatu 60tgaatuutyg ttaaagtaaa aguygauyga yggututggg aggtttgagg uutggygggg 120ygguuuyggg aagtgatttg tgguygutag gygygygutg gaaauuuttt uuuatutgyg 180gaguuuauyg gagutgtgat yggaggagga attuuuuuag guagggagga uyguaggguu 240tttttuauty gtuutgaggg guuutggggu ttggggagua aauutggggt gauuuatttu 300126300DNAArtificial SequenceSynthetic polynucleotide 126gaaatgggtu auuuuaggtt tgutuuuuaa guuuuagggu uuutuaggay gagtgaaaaa 60gguuutgygg tuutuuutgu utgggggaat tuutuutuyg atuauagutu yggtgggutu 120yguagatggg aaagggtttu uagygygygu utagygguua uaaatuautt uuygggguyg 180uuuyguuagg uutuaaauut uuuagaguyg tyggtyggut tttautttaa ygaggattua 240gatgggtuau auuutgtuut uuaaatgygg guutgutuuu yggauuuygu uuagggggut 300127300DNAArtificial SequenceSynthetic polynucleotide 127uatuuauaaa uutuuuaggu uuuutuautu ttuuyguaua gtutguutuy ggtgutuuag 60aaagautgga aatgaggtga gutuuuttgg atuuutguut guuauutgua aatatuatgt 120ggtgutautt guuutuutgt uuutuutuuy gtuuuagguu aatuutuuua uuuuuttaat 180tguuygggga tutuuattau ttaaauuttt uuautggtau ututuutuuu auauaaguut 240uutuagutgt tttuygtutt taauuaauau uttuuutggu tuuagutaut guuauttuat 300128300DNAArtificial SequenceSynthetic polynucleotide 128atgaagtggu agtagutgga guuagggaag gtgttggtta aagayggaaa auagutgagg 60agguttgtgt gggaggagag gtauuagtgg aaaggtttaa gtaatggaga tuuuygggua 120attaaggggg tgggaggatt gguutgggay gggaggaggg auaggagggu aagtaguauu 180auatgatatt tguaggtggu agguagggat uuaagggagu tuauutuatt tuuagtuttt 240utggaguauy ggagguagau tgtgygggaa gagtgagggg guutgggagg tttgtggatg 300129300DNAArtificial SequenceSynthetic polynucleotide 129utttuuuagg autguuttgg uuuuutgguu uuagtutgga ggaututtgu tuauttuutu 60yguuuuuagg tgagutgaga auuuautgyg ygygggautu tgutgyguut guuutuuygg 120gutguagagg guaggaygua uyguuaggua agguygyggu tutgygutga tguuautuyg 180ggagygggtg gutgyggggg aggagggyga guautggayg gggguagygg agtgtagggt 240gtgagatuta aauagagggu tuuautggag gguttguuua gaaggyggua gtuauautgg 300130300DNAArtificial SequenceSynthetic polynucleotide 130uuagtgtgau tguyguuttu tggguaaguu utuuagtgga guuututgtt tagatutuau 60auuutauaut uygutguuuu ygtuuagtgu tyguuutuut uuuuyguagu uauuygutuu 120yggagtggua tuagyguaga guygygguut tguutggygg tgygtuutgu uututguagu 180uygggagggu aggyguagua gagtuuygyg yguagtgggt tutuagutua uutgggggyg 240gaggaagtga guaagagtuu tuuagautgg gguuaggggg uuaagguagt uutgggaaag 300131300DNAArtificial SequenceSynthetic polynucleotide 131tttagggtut ututuuyguu tuttttuutu uuuygutuuu tututuuttg yggutgautu 60uagutuuuuu tyggtguuyg taauuutuut ttuututttt tguyguagtu tuygtututu 120ttuuauaggg tututuuutu uuuututuuu ygtggttgtu agautttutu utggautttu 180tuyguuuygu auyguuyguu uyggatguyg agygtggtag aututguagu ygggutuuty 240gutguuygut ggygutguut auauuuuutt gggutuuuut uuaaggtuuu utuygutygu 300132300DNAArtificial SequenceSynthetic polynucleotide 132gygagyggag gggauuttgg aggggaguuu aagggggtgt agguagyguu agyggguagy 60gaggaguuyg gutguagagt utauuaygut ygguatuygg ggygggyggt gyggggygga 120gaaagtuuag gagaaagtut gauaauuayg gggagagggg gagggagaga uuutgtggaa 180gagagaygga gautgyggua aaaagaggaa aggagggtta yggguauyga gggggagutg 240gagtuaguyg uaaggagaga gggagygggg gaggaaaaga ggygggagag agauuutaaa 300133300DNAArtificial SequenceSynthetic polynucleotide 133gaggguuaua gtaaautgga uaagtttttu tguuuaguut aggutguuau utgtaggtua 60uttgggutuu agutatgtgg utguututtu tgutgggtgu uttaututgg guagtgutgt 120ggttgutuag ggauygguag aguutguuyg uuaguaatgu utttgtuttu atuauyggut 180gtgautuagg utttgggygu uttutgguau tguagutgga uuagagaggu ttuygagtuu 240tgguuagutg uutgauuuuu tuygggguyg aggauutgua gygggtgguu tuutuuyguu 300134300DNAArtificial SequenceSynthetic polynucleotide 134gygggaggag guuauuygut guaggtuuty gguuuyggag ggggtuaggu agutgguuag 60gautyggaag uutututggt uuagutguag tguuagaagg yguuuaaagu utgagtuaua 120guyggtgatg aagauaaagg uattgutggy ggguaggutu tguyggtuuu tgaguaauua 180uaguautguu uagagtaagg uauuuaguag aagagguagu uauatagutg gaguuuaagt 240gauutauagg tgguaguuta ggutggguag aaaaauttgt uuagtttaut gtgguuutua 300135300DNAArtificial SequenceSynthetic polynucleotide 135gttutggutt uatttttttt ttuuuaaaat guuattttua tttgttutta gagttuagaa 60uatgtuaaag aguttuttta aguagtaggt ggttttauag aguuuauaga gaaggaaaau 120taaatatuat uuyggatgua gtuuautayg atygtggagg agtuagatta ututuygggu 180tttgutgtgt utguttgtga aauaggaaag ggagaautga gguaatgagt uauutuautt 240ggguuuaaag uauuauutay gttgaatatg gagaaaatgt gaaguaagag tttuttttta 300136300DNAArtificial SequenceSynthetic polynucleotide 136taaaaagaaa ututtguttu auattttutu uatattuaay gtaggtggtg utttggguuu 60aagtgaggtg autuattguu tuagttutuu utttuutgtt tuauaaguag auauaguaaa 120guuyggagag taatutgaut uutuuaygat ygtagtggau tguatuyggg atgatattta 180gttttuuttu tutgtgggut utgtaaaauu auutautgut taaagaagut utttgauatg 240ttutgaautu taagaauaaa tgaaaatggu attttgggaa aaaaaaaatg aaguuagaau 300137300DNAArtificial SequenceSynthetic polynucleotide 137uutuutuuag tutttguata tatauuaggu tggtatuuat tguaggtggg gauutuutut 60ttgggutttg gaguuuuuut uuutgtgtut utgtauyggg gaguttuttu uttutgtutt 120utuuuttuut tuttgutuat taaaututuy gutuuttaaa auuautuuay gtgtgtuygt 180gttgttttat utaaauyggy gguaggatua agaauuuttg tgttuutgua utuatuagag 240uygtatgata atuaagagut gautauutgg guuattutua tauuattagt guyguattta 300138300DNAArtificial SequenceSynthetic polynucleotide 138taaatgyggu autaatggta tgagaatggu uuaggtagtu agututtgat tatuataygg 60ututgatgag tguaggaaua uaagggttut tgatuutguy guyggtttag ataaaauaau 120ayggauauay gtggagtggt tttaaggagy ggagagttta atgaguaaga aggaagggag 180aagauagaag gaagaagutu uuyggtauag agauauaggg aggggggutu uaaaguuuaa 240agaggaggtu uuuauutgua atggatauua guutggtata tatguaaaga utggaggagg 300139300DNAArtificial SequenceSynthetic polynucleotide 139aaggttaaag tygutgutag auuaagguta aauygtggyg aggtagttgu ttgyguygua 60gagtgtgggt gtgaauagut ggagutuagt ggttuutgga gautuaggga uuauutgtat 120tuuauatuyg guttuuuauu uayguauayg uagtatgauu tgggtttuuu utttatauag 180tggaatguta agtguutaua uuutaguygg ggtuaguuaa utatgguutg tggguauuat 240uuuauutgua guutgttttt gagutaagaa tgttgttgau auttttaaaa auagagaaua 300140300DNAArtificial SequenceSynthetic polynucleotide 140gttututgtt tttaaaagtg tuaauaauat tuttagutua aaaauaggut guaggtggga 60tggtguuuau agguuatagt tggutgauuu yggutagggt gtagguautt aguattuuau 120tgtataaagg ggaaauuuag gtuatautgy gtgtgygtgg gtgggaaguy ggatgtggaa 180tauaggtggt uuutgagtut uuaggaauua utgagutuua gutgttuaua uuuauautut 240gyggyguaag uaautauuty guuayggttt aguuttggtu taguagygau tttaauuttg 300141300DNAArtificial SequenceSynthetic polynucleotide 141gagauagggt ttuautuutg tyguuuaggu tggagtguag uutuaauutu utgggutuag 60tggatuttuu uauutuagau tuutgagtag uygggautau agguauaygu uauuagguut 120agutaatttt ttgtattttt ttgtagagay gaggtttygu taggttguuu aggutggtut 180utaautuutg ggutuaagyg atuuauuuau utuaguttuu uaaagtgutg gggttauagg 240uutgagtuau agygtuyggu tgaaagtgaa gttgaatgag atgautygtu uagguuauat 300142300DNAArtificial SequenceSynthetic polynucleotide 142atgtgguutg gaygagtuat utuattuaau ttuautttua guyggaygut gtgautuagg 60uutgtaauuu uaguautttg ggaagutgag gtgggtggat yguttgaguu uaggagttag 120agauuaguut ggguaauuta gygaaauuty gtututauaa aaaaatauaa aaaattagut 180agguutggtg gygtgtguut gtagtuuygg utautuagga gtutgaggtg ggaagatuua 240utgaguuuag gaggttgagg utguautuua guutgggyga uaggagtgaa auuutgtutu 300143300DNAArtificial SequenceSynthetic polynucleotide 143auayguuauu agguutagut aattttttgt atttttttgt agagaygagg tttygutagg 60ttguuuaggu tggtututaa utuutgggut uaagygatuu auuuauutua guttuuuaaa 120gtgutggggt tauagguutg agtuauagyg tuyggutgaa agtgaagttg aatgagatga 180utygtuuagg uuauatggua atuagtggut gattgayguu aaagttgatt tuattuttut 240uaatgggttu agagtuuaaa ttutggaauu tuagaagayg ttgutattut ggttuuaagu 300144300DNAArtificial SequenceSynthetic polynucleotide 144uttggaauua gaataguaay gtuttutgag gttuuagaat ttggaututg aauuuattga 60gaagaatgaa atuaautttg gygtuaatua guuautgatt guuatgtggu utggaygagt 120uatutuattu aauttuautt tuaguyggay gutgtgautu agguutgtaa uuuuaguaut 180ttgggaagut gaggtgggtg gatyguttga guuuaggagt tagagauuag uutggguaau 240utagygaaau utygtututa uaaaaaaata uaaaaaatta gutagguutg gtggygtgtg 300145300DNAArtificial SequenceSynthetic polynucleotide 145agtgautgua gygtuagguu aaguttgguu auttauatgt utgguatgau agtgguutua 60gagtautygt utgagaagaa gagutatuau utgagygutu tggagaautt aguyggagut 120ttuagguagt utgggaguut auatggaggy gtgtaggutt atgtutuatg tuuaygttgu 180uygggagaua aaatuutttt utatttagag utguuuuaaa atgttutgua uuaguttutu 240autgyggtgg uttuauutta guatauaggt atgtggaygg uuautgtgut ggutuauutt 300146300DNAArtificial SequenceSynthetic polynucleotide 146aaggtgaguu aguauagtgg uygtuuauat auutgtatgu taaggtgaag uuauyguagt 60gagaagutgg tguagaauat tttgggguag ututaaatag aaaaggattt tgtutuuygg 120guaaygtgga uatgagauat aaguutauay guutuuatgt aggutuuuag autguutgaa 180agutuyggut aagttutuua gagygutuag gtgatagutu ttuttutuag aygagtautu 240tgagguuaut gtuatguuag auatgtaagt gguuaagutt gguutgaygu tguagtuaut 300147300DNAArtificial SequenceSynthetic polynucleotide 147yggguauuta ggtutyguuy guutguaguy guutggggay gygggttuyg gayggutggy 60gyggggyggg gyggggauua uygaguagga agtuuuygyg gaagyguygu yggguauagy 120gtgggtgutg tygaggagtg gyguuygggy ggggygggag gttataaata gygguyguua 180tuutguttut uttuagauau auttaattta guygguaggu auayggatgu ttatttttaa 240aaaaagaaut tgttttattg ygutygaggt gauygggaag gtgtuuuygy gggtuautyg 300148300DNAArtificial SequenceSynthetic polynucleotide 148ygagtgauuy gyggggauau uttuuyggtu auutygagyg uaataaaaua agttuttttt 60ttaaaaataa guatuygtgt guutguyggu taaattaagt gtgtutgaag agaaguagga 120tggygguygu tatttataau utuuyguuuy guuygggygu uautuutyga uaguauuuay 180gutgtguuyg gyggyguttu ygyggggaut tuutgutygg tggtuuuygu uuyguuuygy 240guuaguygtu yggaauuygy gtuuuuaggy ggutguaggy gggygagauu taggtguuyg 300149300DNAArtificial SequenceSynthetic polynucleotide 149gaaggtgygg tgyggtgagg tgagaagaga gauygyguta gauuaggyga tgtuttaggg 60aygggagagg ggtgagguuu ayggyggtuu tggggagygg uuuaygauyg guuuayguag 120aguttgtagu uagtgaauag gaagtattgg ygagagggau tgagaaauuu aagagagtgt 180ggggtgagga aaaggtuaag gaagguuuag guttuuagga aggguutggg uyggggyggg 240gygggtggtg ggagguagtg gttaggaygg gygggggtgg gggtgggggt gggggtaggg 300150300DNAArtificial SequenceSynthetic polynucleotide 150uuutauuuuu auuuuuauuu uuauuuuygu uygtuutaau uautguutuu uauuauuygu 60uuyguuuygg uuuagguuut tuutggaagu utggguuttu uttgauuttt tuutuauuuu 120auautututt gggtttutua gtuuututyg uuaatauttu utgttuautg gutauaagut 180utgygtgggu yggtygtggg uygutuuuua ggauyguygt ggguutuauu uututuuygt 240uuutaagaua tyguutggtu tagygyggtu tututtutua uutuauygua uyguauuttu 300151300DNAArtificial SequenceSynthetic polynucleotide 151gagaaauaaa atauattttt taatttaaaa aaaagtauua gaatgaataa aauaggggut 60ttuuaaaaut guttttggta gatttaguaa auutautgaa uttagaaaut ttuattttat 120aattgtuygg agatagaaag uagtguttuy gaataagtgg ataaututgu yggtuuuagt 180aggtguuatt ggtgaguaua uagggttgut taagtututa agtuatttuu utgautgtgg 240tttgaatuaa tgtuaaatat utauaggggt uagguaggta autuaatgaa gtgaaauagg 300152300DNAArtificial SequenceSynthetic polynucleotide 152utgtttuaut tuattgagtt auutguutga uuuutgtaga tatttgauat tgattuaaau 60uauagtuagg gaaatgautt agagauttaa guaauuutgt gtgutuauua atgguauuta 120utgggauygg uagagttatu uauttattyg gaaguautgu tttutatutu yggauaatta 180taaaatgaaa gtttutaagt tuagtaggtt tgutaaatut auuaaaagua gttttggaaa 240guuuutgttt tattuattut ggtauttttt tttaaattaa aaaatgtatt ttgtttutut 300153300DNAArtificial SequenceSynthetic polynucleotide 153ggaggguttu auygtuagyg tagygtaygu utgyggguyg gggygggaga gggauygtyg 60ygtttgtguy guuaguauut gygguuuuua gyguauuygg guuuuaygyg gtaguuuuua 120gggagtgggg agtygggygg gaaauaguty guuygggutu utaygggtgu uuutttyguy 180gygutuuutu uygagggtuu tttguagtyg ggygtggaag tgggatgagu aaauuuygua 240guauaggguu ttyguuuuag gauutguauu ututauyggu uaygggaygt uuutuyguau 300154300DNAArtificial SequenceSynthetic polynucleotide 154gtgyggaggg aygtuuygtg guyggtagag ggtguaggtu utggggygaa gguuutgtgu 60tgyggggttt gutuatuuua uttuuayguu ygautguaaa ggauuutygg gagggagygy 120ggygaaaggg guauuygtag gaguuygggy gagutgtttu uyguuygaut uuuuautuuu 180tgggggutau ygygtggggu uygggtgygu tggggguygu aggtgutggy gguauaaayg 240ygayggtuuu tutuuyguuu ygguuyguag gygtayguta ygutgayggt gaaguuutuu 300155300DNAArtificial SequenceSynthetic polynucleotide 155agauauaaag agggyggaga gauagauaua gaaagaggga gauagygggg utggatggay 60gtgtgguygg guuagtgggg aggagagayg agtuyguaga uagygttuag agguygygut 120guutgggtgu tgaguygtuu yggggttuay ggtyguagtt tgtuuttaua aaayguuuag 180uyguuuygau utgtggtgut tagggaggau utauutggut gtguyggtut gagaaggggu 240uagtgagguu yggtgygggt aygggygggt guagatguag uuaggaggay gggygggagu 300156300DNAArtificial SequenceSynthetic polynucleotide 156gutuuyguuy gtuutuutgg utguatutgu auuyguuygt auuyguauyg gguutuautg 60guuuuttutu agauygguau aguuaggtag gtuutuuuta aguauuauag gtyggggygg 120utgggygttt tgtaaggaua aautgygauy gtgaauuuyg ggayggutua guauuuaggu 180agygygguut utgaaygutg tutgyggaut ygtututuut uuuuautggu uygguuauay 240gtuuatuuag uuuygutgtu tuuututttu tgtgtutgtu tutuyguuut utttgtgtut 300157300DNAArtificial SequenceSynthetic polynucleotide 157gutgtuauau tgagutgttt aauauttaag atgttggtgg atgguaaagu taaaagagua 60utgtaauaua tgauututgg ggutuuygga gtuatgagta uuuuttutag auauaguygt 120gggguuauau agaattutgu tuutgutguy guuyggaagu autuatutgg utuutguauu 180uautuauutg uatuutuuuu utuuuaygag gtgttaagag utgtgggatg agtaaaggag 240guutgtgaag gatttuutgt ttuagtutta uattuaggtu tgagttutua gaggaatutt 300158300DNAArtificial SequenceSynthetic polynucleotide 158aagattuutu tgagaautua gauutgaatg taagautgaa auaggaaatu uttuauaggu 60utuutttaut uatuuuauag ututtaauau utygtgggag ggggaggatg uaggtgagtg 120ggtguaggag uuagatgagt guttuygggy gguaguagga guagaattut gtgtgguuuu 180ayggutgtgt utagaagggg tautuatgau tuygggaguu uuagaggtua tgtgttauag 240tgututttta gutttguuat uuauuaauat uttaagtgtt aaauagutua gtgtgauagu 300159300DNAArtificial SequenceSynthetic polynucleotide 159uagggutggg agaataggat ggauagygtt ttguuagagu utuatgggaa guttuutttu 60agguagutga auuuatttua ggggtaggga guautgatua ggggttggga uattguuuyg 120ggaggaggat gaggatgttt uuagguutyg gutgautuat ggtagtgagt attagtuaut 180uuutuauaag aatuaguuua uatuututag taguututtg tutuuuagag guuuutguuu 240uatgtttauu tguutgaagu tuututuuyg guyguuuuua uuuauatuyg uauagtttgg 300160300DNAArtificial SequenceSynthetic polynucleotide 160uaaautgtgy ggatgtgggt gggggygguy gggagaggag uttuagguag gtaaauatgg 60gguagggguu tutgggagau aagaggutau tagaggatgt gggutgattu ttgtgaggga 120gtgautaata utuautauua tgagtuaguy gagguutgga aauatuutua tuutuutuuy 180gggguaatgt uuuaauuuut gatuagtgut uuutauuuut gaaatgggtt uagutguutg 240aaaggaagut tuuuatgagg ututgguaaa aygutgtuua tuutattutu uuaguuutgu 300161300DNAArtificial SequenceSynthetic polynucleotide 161gaggautaaa agaaguuaga gatgutggtu aattgauaua aaaataaaga gutaagggag 60aggttgagag agggagagua atatutatgg gtgtutggaa tttttaaagg gutuagagga 120ggaggggguy gggygtggtg gutuayguut gttatuygag uautttggga gguuaaggtg 180gguaaatuay gaggtuagga gtttgagagu aguutgauua auatggtgua auuuygtutu 240tautaaaaat auaaaattta guygggtgtg gttgtgtguu tgtaatuuua gutautuagg 300162300DNAArtificial SequenceSynthetic polynucleotide 162uutgagtagu tgggattaua gguauauaau uauauuyggu taaattttgt atttttagta 60gagayggggt tguauuatgt tggtuaggut gututuaaau tuutgauuty gtgatttguu 120uauuttgguu tuuuaaagtg utyggataau aggygtgagu uauuayguuy gguuuuutuu 180tuututgagu uutttaaaaa ttuuagauau uuatagatat tgututuuut ututuaauut 240utuuuttagu tutttatttt tgtgtuaatt gauuaguatu tutgguttut tttagtuutu 300163300DNAArtificial SequenceSynthetic polynucleotide 163uuaggaguuy guutgggagy gyguagygut utaggaguyg agaguygutg uttgguuuty 60gutgguyggg taaauygagg ggaagutuut gguutuuttt uuuttaaguu uuttattgut 120tutgtgggga agguuutuut aggtagaggy gaaggauygg ggagataauu tutuuuatgg 180guuauatuyg utguuatggt utgtgtygtg uuagaaggta uututuaguu utuagtguyg 240tgaaaaatut gauautuaag aaggtygatt gauayguuta aygtyguaua guaatttagt 300164300DNAArtificial SequenceSynthetic polynucleotide 164autaaattgu tgtgygaygt taggygtgtu aatygauutt uttgagtgtu agatttttua 60ygguautgag ggutgagagg tauuttutgg uaygauauag auuatgguag yggatgtggu 120uuatgggaga ggttatutuu uyggtuutty guututauut aggaggguut tuuuuauaga 180aguaataagg gguttaaggg aaaggagguu aggaguttuu uutyggttta uuygguuagy 240gaggguuaag uagyggutut yggutuutag agygutgygy gutuuuaggy gggutuutgg 300165300DNAArtificial SequenceSynthetic polynucleotide 165gagguaygaa gutguyggag utautuagut ttauututag gaaagataua gygaatuauy 60guuaataaaa uaaaguaaaa uaaaaaguty guuatgutga ayggaatggg aaaattgutu 120tuttgtuaut aattttgatt gaattgagty gguaatutut gaauyggttu autgatauaa 180uaataggaaa uatttaautg tttuttguau utttaaauat aaatagtagg tttttaagua 240gtuagtaggy gatgtgtgat uaaggttuag auagayguag auaautgatu auuuautuag 300166299DNAArtificial SequenceSynthetic polynucleotide 166utgagtgggt gatuagttgt utgygtutgt utgaauuttg atuauauaty guutautgau 60tguttaaaaa uutautattt atgtttaaag gtguaagaaa uagttaaatg tttuutattg 120ttgtatuagt gaauyggttu agagattguy gautuaattu aatuaaaatt agtgauaaga 180gaguaatttt uuuattuygt tuaguatggy gagutttttg ttttgutttg ttttattggy 240ggtgattygu tgtatutttu utagaggtaa agutgagtag utuygguagu ttygtguut

299167300DNAArtificial SequenceSynthetic polynucleotide 167gauutuagut uygggtgaua uyggtgggyg tygggtgtgg uutuagauag utuuuttuut 60uuuyggutgg ttguuaggtu aauauygggt gggautaguu tutggtgtyg guagtaguuu 120uatgutuuyg guutttgggt tuttguatgy guygtuuuua tuauutggut guuuututua 180uttuygtutu uauutgtuuy gggtuauutg tuuttuaagu uagaaattaa ggauaguauu 240uuutuuuaga uyguutggut guagtuuygg gatgggygut uutagtyguu tagatygggu 300168300DNAArtificial SequenceSynthetic polynucleotide 168guuygatuta ggygautagg agyguuuatu uygggautgu aguuaggygg tutgggaggg 60ggtgutgtuu ttaatttutg guttgaagga uaggtgauuy gggauaggtg gagayggaag 120tgagaggggu aguuaggtga tggggayggy guatguaaga auuuaaaggu ygggaguatg 180gggutautgu ygauauuaga ggutagtuuu auuyggtgtt gauutgguaa uuaguygggg 240aggaagggag utgtutgagg uuauauuyga yguuuauygg tgtuauuygg agutgaggtu 300169300DNAArtificial SequenceSynthetic polynucleotide 169gtatutgtgt uaauuagygg ttutuaguut gguutuatuu aggguutgaa guutautaua 60gaauuuuuag uaguaygtgg ggtguauagu aaagatuagu uutggauaua guygggtgut 120uagggygggg tgagggggua ggagguagga yguaggaggt gagutgtuyg ggygggguag 180gatgagggag tuutguattg uagagutaag ggggagaatu atuaguauuu taattagutu 240ttgatggutt uuaaaguutt ttaagtuutt tttttttttt ttttttttta tuuutauaag 300170300DNAArtificial SequenceSynthetic polynucleotide 170uttgtaggga taaaaaaaaa aaaaaaaaaa aaggauttaa aaggutttgg aaguuatuaa 60gagutaatta gggtgutgat gattutuuuu uttagututg uaatguagga utuuutuatu 120utguuuyguu yggauagutu auutuutgyg tuutguutuu tguuuuutua uuuyguuutg 180aguauuyggu tgtgtuuagg gutgatuttt gutgtguauu uuaygtgutg utgggggttu 240tgtagtaggu ttuagguuut ggatgagguu aggutgagaa uygutggttg auauagatau 300171300DNAArtificial SequenceSynthetic polynucleotide 171gattaauttg uutuutgaua agtuatauuu tttaguttag tautaaggua gaagagaguu 60utgttgaaga guuyguttgt gttutgtggt aaagauauag guutauyggu ttutuygtgg 120gtuuuagtgu tgagaagggu auaggutggu tggagauagt guuutguttg auagauuuut 180uuaygutygg atuuttuuag tutguauygg uuauutguau tggtttuayg gaagagutag 240aattutgttt taatgttggu uagtttuuat uattaguttg aaaagaauau agaauttayg 300172300DNAArtificial SequenceSynthetic polynucleotide 172ygtaagttut gtgttutttt uaagutaatg atggaaautg guuaauatta aaauagaatt 60utagututtu ygtgaaauua gtguaggtgg uyggtguaga utggaaggat uygagygtgg 120aggggtutgt uaaguagggu autgtutuua guuaguutgt guuuttutua guautgggau 180uuayggagaa guyggtaggu utgtgtuttt auuauagaau auaagygggu tuttuaauag 240ggutututtu tguuttagta utaagutaaa gggtatgaut tgtuaggagg uaagttaatu 300173300DNAArtificial SequenceSynthetic polynucleotide 173gauuauaggt gtgtgutatu atguuygggt aatttttata ttttttggtu tuautatgtt 60guuuaggutg gtutuaaaut uutgggutua agtgatuutu utguutuagu utuuuaaagt 120gttggattag agguatgagu uauuttguay gtttguutuu tgauutuagg tuuuuaygga 180gttggtuatu ttutggguut ygutuaguyg gtgutgaagg tgagtuatgu tygatgatga 240uutgaggagu agaagaaggt guaggtgagt uauutgaggg gaautgggtu atgauuagag 300174300DNAArtificial SequenceSynthetic polynucleotide 174ututggtuat gauuuagttu uuutuaggtg autuauutgu auuttuttut gutuutuagg 60tuatuatyga guatgautua uuttuaguau yggutgagyg agguuuagaa gatgauuaau 120tuygtgggga uutgaggtua ggagguaaay gtguaaggtg gutuatguut utaatuuaau 180autttgggag gutgagguag gaggatuaut tgaguuuagg agtttgagau uaguutgggu 240aauatagtga gauuaaaaaa tataaaaatt auuyggguat gataguauau auutgtggtu 300175300DNAArtificial SequenceSynthetic polynucleotide 175aggaagtyga gguttagaag ttgggtgaut tgtuaaaggt yguuauuuay ggtgaggguu 60aggttutggg agggutgagg gguagguatg gtgaguuagt tuyggguatg agguaaggyg 120tgguagguut ggggguaaaa guuauaguuy gtgtggaggg ggtgggggga tygagguutt 180tgggaaguut gtggattutg gutguagtgt gggtgtgaua utgagtgutu yggggautuy 240gagttatuau uuagguautg guuaguuuua ygutuuutuu tuuaggtaut tggutuuutg 300176300DNAArtificial SequenceSynthetic polynucleotide 176agggaguuaa gtauutggag gagggagygt ggggutgguu agtguutggg tgataautyg 60gagtuuuygg aguautuagt gtuauauuua uautguaguu agaatuuaua gguttuuuaa 120agguutygat uuuuuuauuu uutuuauayg ggutgtggut tttguuuuua gguutguuay 180guuttguutu atguuyggaa utggutuauu atguutguuu utuaguuutu uuagaauutg 240guuutuauyg tgggtggyga uutttgauaa gtuauuuaau ttutaaguut ygauttuutu 300177300DNAArtificial SequenceSynthetic polynucleotide 177aguuayggyg auuauuaggt uuatuutuuu uuauutuutu utuutguagg tgguuttutg 60guuagtgtgu utgagtgutu auututtgut utagtgtuut ggtgutuygg ututuututt 120uutuutuaut utuutggguu tggguutguy gutuuygggu utuuaggtut agauauaagg 180gttgaatgau uagautgutg gtutgttuag tttuuatgtg guutygguuu auuuuagutu 240tggutguutu uuuaaagtut uaatuaygay gagatuatau agtaaututg uuuuutuuut 300178300DNAArtificial SequenceSynthetic polynucleotide 178agggaggggg uagagttaut gtatgatuty gtygtgattg agautttggg gagguaguua 60gagutggggt ggguygaggu uauatggaaa utgaauagau uaguagtutg gtuattuaau 120uuttgtgtut agauutggag guuygggagy gguagguuua gguuuaggag agtgaggagg 180aagaggagag uyggaguauu aggauautag aguaagaggt gaguautuag guauautggu 240uagaagguua uutguaggag gaggaggtgg gggaggatgg auutggtggt yguygtggut 300179300DNAArtificial SequenceSynthetic polynucleotide 179aaggtgaatg utguaauuut ututuutuag uuutguaguy gatuuutgau ataaautuut 60tgaagttuag tgguututtt uuatguauut auuauutaua uutgutgutt tuaaagaaau 120uauaauutgg auygggaaua gaautggayg tguuaaaatg uutgaggaua uttuatygaa 180tgtggutggu ttgatgggaa gutgguatga utagaaatgt uaggagtutt uuututygag 240gtttuaagut ttgtgtttut gautuaatgg tuyggattga gatuagatga gtuaagttua 300180300DNAArtificial SequenceSynthetic polynucleotide 180gaauttgaut uatutgatut uaatuyggau uattgagtua gaaauauaaa guttgaaauu 60tygagaggga agautuutga uatttutagt uatguuagut tuuuatuaag uuaguuauat 120tygatgaagt gtuutuaggu attttgguay gtuuagttut gttuuyggtu uaggttgtgg 180tttutttgaa aguaguaggt gtaggtggta ggtguatgga aagagguuau tgaauttuaa 240ggagtttatg tuagggatyg gutguagggu tgaggagaga gggttguagu attuauuttu 300181300DNAArtificial SequenceSynthetic polynucleotide 181uaguuutgua guygatuuut gauataaaut uuttgaagtt uagtgguutu tttuuatgua 60uutauuauut auauutgutg utttuaaaga aauuauaauu tggauyggga auagaautgg 120aygtguuaaa atguutgagg auauttuaty gaatgtggut gguttgatgg gaagutggua 180tgautagaaa tgtuaggagt uttuuututy gaggtttuaa gutttgtgtt tutgautuaa 240tggtuyggat tgagatuaga tgagtuaagt tuagatgauu atguaaauut ttagatgggg 300182300DNAArtificial SequenceSynthetic polynucleotide 182uuuuatutaa aggtttguat ggtuatutga auttgautua tutgatutua atuyggauua 60ttgagtuaga aauauaaagu ttgaaauuty gagagggaag autuutgaua tttutagtua 120tguuaguttu uuatuaaguu aguuauatty gatgaagtgt uutuagguat tttgguaygt 180uuagttutgt tuuyggtuua ggttgtggtt tutttgaaag uaguaggtgt aggtggtagg 240tguatggaaa gagguuautg aauttuaagg agtttatgtu agggatyggu tguagggutg 300183300DNAArtificial SequenceSynthetic polynucleotide 183uutauuauut auauutgutg utttuaaaga aauuauaauu tggauyggga auagaautgg 60aygtguuaaa atguutgagg auauttuaty gaatgtggut gguttgatgg gaagutggua 120tgautagaaa tgtuaggagt uttuuututy gaggtttuaa gutttgtgtt tutgautuaa 180tggtuyggat tgagatuaga tgagtuaagt tuagatgauu atguaaauut ttagatgggg 240uutaaaauua aatutgtgtt utuaaauuat tuuaaatgtg ttuatuauua gttatagttt 300184300DNAArtificial SequenceSynthetic polynucleotide 184aaautataau tggtgatgaa uauatttgga atggtttgag aauauagatt tggttttagg 60uuuuatutaa aggtttguat ggtuatutga auttgautua tutgatutua atuyggauua 120ttgagtuaga aauauaaagu ttgaaauuty gagagggaag autuutgaua tttutagtua 180tguuaguttu uuatuaaguu aguuauatty gatgaagtgt uutuagguat tttgguaygt 240uuagttutgt tuuyggtuua ggttgtggtt tutttgaaag uaguaggtgt aggtggtagg 300185300DNAArtificial SequenceSynthetic polynucleotide 185gagaggggaa gggguygauu auutgutuuy gaguuattut ygggutyggu uaguuattgg 60gutgggaauu tgtuaatuut ggttgatutt uuaatgagut gtgaautggt uttuygggag 120gauttauagg aggutggaaa ygggguutgg ygygyguttu uututuagtg ygaggutgau 180tggttggaut yguygggutu tautgtgggu uuuaygutat gtttagaygu uygaygtgtu 240uuattttatt gaautygtuu tguuuuuuaa gtagggayga tttauutuua ttttutagat 300186300DNAArtificial SequenceSynthetic polynucleotide 186atutagaaaa tggaggtaaa tygtuuutau ttggggggua ggaygagttu aataaaatgg 60gauaygtygg gygtutaaau atagygtggg guuuauagta gaguuyggyg agtuuaauua 120gtuaguutyg uautgagagg gaagygygyg uuagguuuyg tttuuaguut uutgtaagtu 180utuuyggaag auuagttuau agutuattgg aagatuaauu aggattgaua ggttuuuagu 240uuaatggutg guygaguuyg agaatgguty gggaguaggt ggtygguuuu ttuuuututu 300187300DNAArtificial SequenceSynthetic polynucleotide 187yggggguagg gaguagauut gautuagtgg ygtuagtgut auttuaaagy gguagyguat 60ttuattaaaa atutgatgta gaaattauuu tgggutttgt tttguaaaga guatttguat 120aagaaaaaat aatuaguygg ttaattuuuu ygtuuautgg uaggaagaga gauaguuttu 180agagagtttg ggautututu attuuyggag aattaaaagu utuygagaua tuuattttag 240aagttutggt uaatygttut taaagtgygg tuagaagauu uuttgygtut gaatggtttg 300188300DNAArtificial SequenceSynthetic polynucleotide 188uaaauuattu agayguaagg ggtuttutga uyguauttta agaaygattg auuagaautt 60utaaaatgga tgtutyggag guttttaatt utuygggaat gagagagtuu uaaaututut 120gaaggutgtu tututtuutg uuagtggayg ggggaattaa uyggutgatt attttttutt 180atguaaatgu tutttguaaa auaaaguuua gggtaatttu tauatuagat ttttaatgaa 240atgygutguy gutttgaagt aguautgayg uuautgagtu aggtutgutu uutguuuuyg 300189300DNAArtificial SequenceSynthetic polynucleotide 189uagtgttgta gauutattaa ttatuaggat aattayggay ggggaaatuu agauauagat 60auaatuagtg uuutuutuua uutuuuygua uayguuuutu uyggtutuuu tgauatuutg 120gtgtguautg tgttuuuutg uuatutuuay gutgyggutu utautagauu uauuuutguy 180ggtguuaaaa tguuuaaagg aaggutgagt uatgututgg uutguuuagu yguaatagtu 240atgutguaau tuuuayggaa aauutuuttt uauuuautuu agaggtutga gauauuutaa 300190300DNAArtificial SequenceSynthetic polynucleotide 190ttagggtgtu tuagauutut ggagtgggtg aaaggaggtt ttuygtggga gttguaguat 60gautattgyg gutggguagg uuagaguatg autuaguutt uutttgggua ttttgguauy 120gguaggggtg ggtutagtag gaguyguagy gtggagatgg uaggggaaua uagtguauau 180uaggatgtua gggagauygg gaggggygtg tgyggggagg tggaggaggg uautgattgt 240atutgtgtut ggatttuuuy gtuygtaatt atuutgataa ttaataggtu tauaauautg 300191300DNAArtificial SequenceSynthetic polynucleotide 191ggaaggagyg aguttutttt tataggagut uuagttuuty gttttgttut uttygggtta 60ttutuuaaag aaaguyggut uttgagtuag utgguaggag agygaggyga atgygutggt 120gutgguygua atgguuuygg ttuaayguty gutuuagutg gtuaygtuut uauyggggyg 180guyggygguu tguutguuua ygututguua ggaguuuagg tuaguuuttg uutyguyggg 240guyggaguuy gtuuaaaatu aauaagtutt ttgtguutut uutttggayg utgtataatt 300192300DNAArtificial SequenceSynthetic polynucleotide 192aattatauag ygtuuaaagg agagguauaa aagauttgtt gattttggay gggutuyggu 60uuyggygagg uaagggutga uutgggutuu tgguagagyg tggguaggua gguyguyggu 120yguuuyggtg aggaygtgau uagutggagy gagygttgaa uygggguuat tgygguuagu 180auuagyguat tyguutygut utuutguuag utgautuaag aguygguttt utttggagaa 240taauuygaag agaauaaaay gaggaautgg agutuutata aaaagaagut ygutuuttuu 300193300DNAArtificial SequenceSynthetic polynucleotide 193utggttgtgg aaggagygag ututuygtuu uygggagtat guaagtttgg gutguaygat 60uauttggaag ggattgggyg gagttutgtu atttggagaa agggtuutgg gaguttuagg 120tttgtgtagg gygaggaygg ggyggttutg ygtuygguua ggttgguuut ygaggauuua 180guygtuuuua auutuutaaa utgutgtygg atgtagaaga utyguattua utgututuua 240uagtyggtga agggagaayg uygaaaaggg uyguattuuu tuutguyggt uuuutuuuut 300194300DNAArtificial SequenceSynthetic polynucleotide 194aggggagggg auygguagga gggaatgygg uuuttttygg ygttutuuut tuauygautg 60tggagaguag tgaatgygag tuttutauat uygauaguag tttaggaggt tggggayggu 120tgggtuutyg aggguuaauu tgguyggayg uagaauyguu uygtuutygu uutauauaaa 180uutgaagutu uuaggauuut ttutuuaaat gauagaautu yguuuaatuu uttuuaagtg 240atygtguagu uuaaauttgu atautuuygg ggayggagag utygutuutt uuauaauuag 300195300DNAArtificial SequenceSynthetic polynucleotide 195gggtgtuagg utauuuttga agggauutau utuutuuagu uautguuaut ggauuutuuu 60tuaguuuutu taguaaagua guuuuaatgu atgtuutgag attgtuuygg aaaautgtua 120utuagagggg aagaututtg gguauagagu ygttatttat aauaguaaga uautguaggu 180tguutaaaua utuuaygaua gagatgaygg aguaattuay gguauuuutg uuaagagagt 240attauauagu uattaaaaat gatuaaguag agauyggtag tgaygutgag taatgttttu 300196300DNAArtificial SequenceSynthetic polynucleotide 196gaaaauatta utuagygtua utauyggtut utguttgatu atttttaatg gutgtgtaat 60autututtgg uaggggtguy gtgaattgut uygtuatutu tgtygtggag tgtttaggua 120guutguagtg tuttgutgtt ataaataayg gututgtguu uaagagtutt uuuututgag 180tgauagtttt uygggauaat utuaggauat guattggggu tgutttguta gaggggutga 240gggagggtuu agtgguagtg gutggaggag gtaggtuuut tuaagggtag uutgauauuu 300197300DNAArtificial SequenceSynthetic polynucleotide 197guuuauygyg gaggguuuuu utatuutuut uatuutuaut ggutuauuua ggguauuauu 60auutuutuua ggaaauuutu uutguuuuut atututgggt gtutuauauu utggguauut 120auaguuagaa uuuuauutuy ggguuutuyg tttuuagtgg utgagtagga guttuagttt 180taggagautu uuutgaguag aauygauuuu tuttuatutt uuuaauuuuu auuuauauau 240tuaggautgg gtauyggggu utguuuuaat ttguaggutt agagtuaggg gttagggtgg 300198300DNAArtificial SequenceSynthetic polynucleotide 198uauuutaauu uutgaututa aguutguaaa ttgggguagg uuuyggtauu uagtuutgag 60tgtgtgggtg ggggttggga agatgaagag gggtyggttu tgutuagggg agtutuutaa 120aautgaagut uutautuagu uautggaaay ggaggguuyg gaggtggggt tutggutgta 180ggtguuuagg gtgtgagaua uuuagagata ggggguaggg agggtttuut ggaggaggtg 240gtggtguuut gggtgaguua gtgaggatga ggaggatagg gggguuutuy gyggtgggua 300199300DNAArtificial SequenceSynthetic polynucleotide 199uttaaatgag aagaauatgt ttutauauyg uatttgtgaa agtttgguty ggagutaygy 60gutgattaat atuagatutu uttuautygu utyguuauaa tuttgtuaua tutggutgau 120aaatuuygag gaautuyggu aaaguuaggy ggyggygggg utuygggtut gggyggyggu 180tuyggaggag uagygggaga uuuyguagyg guutuutuut tutuyguuyg ygguuuuuag 240uutyguyguy guyguuyggu tuuuaguayg gaauygaygg ggygutuuyg agaygggyga 300200300DNAArtificial SequenceSynthetic polynucleotide 200tyguuygtut ygggagyguu uygtyggttu ygtgutggga guygggyggy ggyggygagg 60utggggguyg ygggyggaga aggaggaggu ygutgygggg tutuuygutg utuutuygga 120guyguyguuu agauuyggag uuuyguyguy guutgguttt guyggagttu utygggattt 180gtuaguuaga tgtgauaaga ttgtggygag gygagtgaag gagatutgat attaatuagy 240gygtagutuy gaguuaaaut ttuauaaatg yggtgtagaa auatgttutt utuatttaag 300201300DNAArtificial SequenceSynthetic polynucleotide 201gtggtaggtu tgtgtggaga uttgaatuut gttttutuuu aguuttttuu auuaaggaua 60uuuaggagag uaaggatatg guuagaggag aggtggtgtt uuuututtga utggguuutg 120ututuaguuu uauaggtgat uyggaagatt ygggtggagu agtttuutga tguutuyggt 180aguutgaagu tgtggtguua gtttttuaau attuttagtg autuagtutt gauatggguu 240aaggatuagy guuuagtggg ygaggtgggu aggaggtaag uuaaygauau uautguuauu 300202300DNAArtificial SequenceSynthetic polynucleotide 202ggtgguagtg gtgtygttgg uttauutuut guuuauutyg uuuautgggy gutgatuutt 60gguuuatgtu aagautgagt uautaagaat gttgaaaaau tgguauuaua guttuaggut 120auyggaggua tuaggaaaut gutuuauuyg aatuttuygg atuauutgtg gggutgagag 180uaggguuuag tuaagagggg aauauuauut utuututggu uatatuuttg ututuutggg 240tgtuuttggt ggaaaaggut gggagaaaau aggattuaag tutuuauaua gauutauuau 300203300DNAArtificial SequenceSynthetic polynucleotide 203tguutauuau auutygtggg tgaaauagat atttygagua tgautgagut tattaagagu 60uutgyggygu ttuututguy gggggtttag aaatttuaaa ggatgggggt tgagggaggg 120aggagttatg gguatgtgat gtggauaggg yggguaggag gatggaagta auaggtuuaa 180aatgtatutt tggtgguuyg guagagutut tguatggggt gagaatggta atttaggaag 240aguaagtutt uuuatutgtg aaguagaaga aaaaagtgga uttaaggaga agttygggtg 300204300DNAArtificial SequenceSynthetic polynucleotide 204uauuygaaut tutuuttaag tuuauttttt tuttutgutt uauagatggg aagauttgut 60uttuutaaat tauuattutu auuuuatgua agagututgu yggguuauua aagatauatt 120ttggauutgt tauttuuatu utuutguuyg uuutgtuuau atuauatguu uataautuut 180uuutuuutua auuuuuatuu tttgaaattt utaaauuuuy gguagaggaa gyguyguagg 240gututtaata agutuagtua tgutygaaat atutgtttua uuuaygaggt gtggtaggua 300205300DNAArtificial SequenceSynthetic polynucleotide 205gaguuaauut utuutttuat tuutggaggt gggggauuyg uuutuatutu agguutgaag 60agggutgtgt gtgagttutu uauttgtgtg tggggtgagu uygguuuatg uauauaguta 120uauauauatu auauauuuau auuyggauay gyguutuagg tuuuuauaut guuuttauau 180auatgyguuu utuauauatg uatgtuuuut ttguauauay guuuuutygu auayguatgu 240uuuutyguau ayguatguau auaggutuau tutgutguut gtuuutggut gutgtgtgut 300206300DNAArtificial SequenceSynthetic polynucleotide 206aguauauagu aguuagggau agguaguaga gtgaguutgt gtguatgygt gtgygagggg 60guatgygtgt gygagggggy gtgtgtguaa aggggauatg uatgtgtgag gggyguatgt 120gtgtaagggu agtgtgggga uutgaggygy gtgtuygggt gtgggtgtgt gatgtgtgtg 180tagutgtgtg uatggguygg gutuauuuua uauauaagtg gagaautuau auauaguuut 240uttuagguut gagatgaggg ygggtuuuuu auutuuagga atgaaaggag aggttggutu 300207300DNAArtificial SequenceSynthetic polynucleotide 207uuuayggggg uagguauygg agggggtguu uauagaggat agaggayguy gagaagtgau 60utggggaguu ataggatgag gaagagagaa gagatgauag uaggggutgt aggaggtuau 120uutuuaygga gggaggggtg aygguagagg ygtuyguagg agutggtauy ggtggggutg 180uuuuuagggg gggutgauag agguaguaau tgaguaggua ggggtggagy gaggtguuag 240uutguygtgg aaaggagayg uuaguagygg gggguuutuu tggggtuuua gtuutgutut 300208300DNAArtificial SequenceSynthetic polynucleotide 208agaguaggau tgggauuuua ggaggguuuu uygutgutgg ygtutuuttt uuaygguagg 60utgguauuty gutuuauuuu tguutgutua gttgutguut utgtuaguuu uuuutggggg 120uaguuuuauy ggtauuagut uutgyggayg uututguygt uauuuutuuu tuygtggagg 180gtgauutuut auaguuuutg utgtuatutu ttutututtu utuatuutat ggutuuuuag 240gtuauttuty

ggygtuutut atuututgtg gguauuuuut uyggtguutg uuuuygtggg 300209300DNAArtificial SequenceSynthetic polynucleotide 209tgauautuag gatuuaaaag utaguuutgu uuauuuuagu uuutggauut guttauutgg 60gtgtguauut gutuyggggg gtggaggtgu tuuuuauagt uyggguuagg auaguutuag 120gggagagtga agguutguag gaggguaggy gagauaagga gggtgtuuag ggutagggag 180tguyggatga aauuagutut gtuuutgtgu aggutuuagg utuuyguutg auaaauaggu 240agggaguuau agtuagggau aataaaaaut tggtguautu tgaaaguagu auttggauag 300210300DNAArtificial SequenceSynthetic polynucleotide 210tgtuuaagtg utgutttuag agtguauuaa gtttttattg tuuutgautg tggutuuutg 60uutgtttgtu aggygggagu utggaguutg uauagggaua gagutggttt uatuygguau 120tuuutaguuu tggauauuut uuttgtutyg uutguuutuu tguagguutt uaututuuuu 180tgaggutgtu utgguuygga utgtggggag uauutuuauu uuuyggagua ggtguauauu 240uaggtaagua ggtuuagggg utggggtggg uagggutagu ttttggatuu tgagtgtuau 300211300DNAArtificial SequenceSynthetic polynucleotide 211uaaataagta gttauutuag aagtuautta ygtaaaagau tuattuuuua aaayguuagg 60uauatggatt atuautgtgt tattuaayga ygatauaatg guauagaatg tatuatautg 120agaagtgagt guuututuyg ggauatauty gtuagtgagt uatuuaguau tagaauautg 180gagatataaa taaatauuau ututtutaaa auagtutgaa attuaagtgg tuataauuta 240gaguatuatg guyggguatg gtggutuatg uutgtaauuu uaguatgagg utgagatggg 300212300DNAArtificial SequenceSynthetic polynucleotide 212uuatutuagu utuatgutgg ggttauaggu atgaguuauu atguuygguu atgatgutut 60aggttatgau uauttgaatt tuagautgtt ttagaagagg tggtatttat ttatatutuu 120agtgttutag tgutggatga utuautgayg agtatgtuuy ggagagggua utuauttutu 180agtatgatau attutgtguu attgtatygt ygttgaataa uauagtgata atuuatgtgu 240utggygtttt ggggaatgag tuttttaygt aagtgauttu tgaggtaaut auttatttga 300213300DNAArtificial SequenceSynthetic polynucleotide 213gtuutuauat ttgautuygg ataaauutut tuaaatattt tauagautut ggutttutyg 60ttaauaagua gutuauauat atagtgtutu aguagtgaua gatgutgguu uauuuygagg 120tuaggatgau tuaguaggga ttgagtttgy gggygtuatg utuuaagguu yggaatagga 180ggttggtgut uattuutuau atagtgggua aatuutaggg uaggggaggg gggguaatgu 240uagagaatgg tuuuuauutg gggyggtutg aygguuagag atguagagaa agagayguut 300214300DNAArtificial SequenceSynthetic polynucleotide 214aggygtutut ttututguat ututgguygt uagauyguuu uaggtgggga uuattututg 60guattguuuu uuutuuuutg uuutaggatt tguuuautat gtgaggaatg aguauuaauu 120tuutattuyg gguuttggag uatgayguuy guaaautuaa tuuutgutga gtuatuutga 180uutyggggtg gguuaguatu tgtuautgut gagauautat atgtgtgagu tguttgttaa 240ygagaaaguu agagtutgta aaatatttga agaggtttat uyggagtuaa atgtgaggau 300215299DNAArtificial SequenceSynthetic polynucleotide 215gaaaguaguu ututuuutgu uutgtaaggt gatuuuygat uygggaattu uuauttutga 60aggaygttut ggaaaagtgu auagattaau tgagattuut guttutggat uaaguautuu 120tgauautaty gttuygattt tutaaaaaag agattgtggu aaaatutauu tygtgagatu 180agaaaatgua guagggatga atuauygguu ututuagauu tuauuaguut uuagguuatt 240uutaagaguu tuautuutuy gttutgttgg uagtggggga ggtayggggu yggatggua 299216300DNAArtificial SequenceSynthetic polynucleotide 216tguuatuygg uuuygtauut uuuuuautgu uaauagaayg gaggagtgag gututtagga 60atgguutgga ggutggtgag gtutgagagg guyggtgatt uatuuutgut guattttutg 120atutuauyga ggtagatttt guuauaatut uttttttaga aaatyggaay gatagtgtua 180ggagtguttg atuuagaagu aggaatutua gttaatutgt guauttttuu agaaygtuut 240tuagaagtgg gaattuuygg atyggggatu auuttauagg guagggagag ggutgutttu 300217300DNAArtificial SequenceSynthetic polynucleotide 217aagaaaagag aaaguuuatu uaggtaaggg uaguutggtg autattauuu tggggagaut 60uuuuauuuau autguuautu uaggutuauu ygagggutgu aguttuutuy ggatggatuu 120agggygguta utggtuuuag agutgggggu tgagtggguu ygtguygagg gutgtggygt 180utgauaaguy ggutuuuaut gtgaguaggg aagggyggat gggygggggu uayggutguu 240utggutuuuu auuutgutgt guttututut autuuuutgu uutguutuut aauauuuagt 300218300DNAArtificial SequenceSynthetic polynucleotide 218autgggtgtt aggagguagg guaggggagt agagagaagu auaguagggt ggggaguuag 60gguaguygtg guuuuyguuu atuyguuutt uuutgutuau agtgggaguy gguttgtuag 120ayguuauagu uutygguayg gguuuautua guuuuuagut utgggauuag taguyguuut 180ggatuuatuy ggaggaagut guaguuutyg ggtgaguutg gagtgguagt gtgggtgggg 240agtutuuuua gggtaatagt uauuaggutg uuuttauutg gatggguttt ututtttutt 300219300DNAArtificial SequenceSynthetic polynucleotide 219utgagguagg gutguaggut uaggaggagg agatgggtgg agagagaaua agutuauuuy 60gggagggtga utauaggaga aatggguuuu tuaagtatgu tgatttuygu utuautgutg 120uutgututtu yguuuauutu yggututggu tuatutgutu ttgtaaguag ggtuutgggu 180tgggtgutgu aggyguatga ggaaagtggg aguygggayg ggguagutua ggguayguuu 240tuuaauautg ygutuygagg auutuagygg ttttautuag gggtguuaut gagguauagu 300220300DNAArtificial SequenceSynthetic polynucleotide 220gutgtguutu agtgguauuu utgagtaaaa uygutgaggt uutyggagyg uagtgttgga 60gggygtguuu tgagutguuu ygtuuyggut uuuautttuu tuatgyguut guaguauuua 120guuuaggauu utguttauaa gaguagatga guuagaguyg gaggtgggyg gaagaguagg 180uaguagtgag gyggaaatua guatauttga gggguuuatt tutuutgtag tuauuutuuy 240ggggtgagut tgttututut uuauuuatut uutuutuutg aguutguagu uutguutuag 300221300DNAArtificial SequenceSynthetic polynucleotide 221guuuaggutg gagtguagtg gygtgatutt ggutuautgu aauututguu tuuygggttu 60aagygattut uutguutuag uutuuuagat auutgggatt auaggtgtgt gauauuatau 120uuagutaatt tttgtatttt tagtagagay gguuatgtta gtuaggutgg tuttgaautu 180utgauutuag tgattuauyg guutuaguuu uuaaagtgut ggtattatag tuatgaguua 240utguauuygg uututguttt tguttuutta gtgguatuuu autguuttgu tttuaauatt 300222300DNAArtificial SequenceSynthetic polynucleotide 222aatgttgaaa guaagguagt gggatguuau taaggaagua aaaguagagg uygggtguag 60tggutuatga utataatauu aguautttgg gggutgaggu yggtgaatua utgaggtuag 120gagttuaaga uuaguutgau taauatgguy gtututauta aaaatauaaa aattagutgg 180gtatggtgtu auauauutgt aatuuuaggt atutgggagg utgagguagg agaatygutt 240gaauuyggga gguagaggtt guagtgaguu aagatuaygu uautguautu uaguutgggu 300223300DNAArtificial SequenceSynthetic polynucleotide 223guuaututat aaaaatgaag aguagaguty gagtguttat aauaygtuat ttttauuuaa 60gauagagaag aaaaaygaaa gagaguutga guattuuttt gautuuutuu auuuuyggaa 120ggtatattua gagtutuuaa gautguutuy guuuautuau atgtttatgg uuyggtgaga 180uyguatuutu uutttutata tutgtuuutt ttutggatgu agggauauag aatuuuutaa 240gtgggaagag utttggagtg gaggutgttu aaagttutgt ggtgattaat tattauutau 300224300DNAArtificial SequenceSynthetic polynucleotide 224taggtaataa ttaatuauua uagaautttg aauaguutuu autuuaaagu tuttuuuaut 60taggggattu tgtgtuuutg uatuuagaaa agggauagat atagaaaggg aggatgyggt 120utuauygggu uataaauatg tgagtgggyg gagguagtut tggagautut gaatatauut 180tuygggggtg gagggagtua aaggaatgut uaggututut ttygtttttu ttututgtut 240tgggtaaaaa tgaygtgtta taaguautyg agututgutu ttuattttta tagagtggut 300225300DNAArtificial SequenceSynthetic polynucleotide 225attaaaauag uaaautuuag guuuaaagta ggtttuagtu tutattaaga taauaaaagg 60tuutaaatgu uagguutggg yguaaautgt guagauaagy gggtgguygg agaaggaggg 120gggtuaagga agagagggaa autuaattga yggttauttt tttttuagag ttatttuygg 180tgggtutguu uuuauuuutu aauaaatttt gttgututga guattuuagg uataaaaagt 240gagguuutgg aggguuuutg agauuagygt uutguauagt gauatgguau agtgauatgg 300226300DNAArtificial SequenceSynthetic polynucleotide 226uuatgtuaut gtguuatgtu autgtguagg aygutggtut uagggguuut uuaggguutu 60autttttatg uutggaatgu tuagaguaau aaaatttgtt gaggggtggg gguagauuua 120uyggaaataa ututgaaaaa aaagtaauyg tuaattgagt ttuuututut tuuttgauuu 180uuutuuttut uygguuauuy guttgtutgu auagtttgyg uuuagguutg guatttagga 240uuttttgtta tuttaataga gautgaaauu tautttgggu utggagtttg utgttttaat 300227300DNAArtificial SequenceSynthetic polynucleotide 227ggututgaga gtgutggaau uaauyggayg gggtuaguuu uauuatggga uutgguygat 60gagtuatutu tutgaaggyg tuttuuuttu tgtgaagtgg ggaaggtaau tgtuatuuua 120uagggygatt gtggguauuy gggagauuyg utgagggatg utguagtgta gaaguttuuu 180aaatutaygu tguttututt uutuutuagt uututuuygu tgutguuutu yggttuatgu 240uutgtggutg atuuatuauy ggututuuay gguuttuauu ttgggygggt tggatggutg 300228300DNAArtificial SequenceSynthetic polynucleotide 228aguuatuuaa uuyguuuaag gtgaagguyg tggagaguyg gtgatggatu aguuauaggg 60uatgaauygg aggguaguag ygggagagga utgaggagga agagaaguag ygtagatttg 120ggaaguttut auautguagu atuuutuagy gggtutuuyg ggtguuuaua atyguuutgt 180gggatgauag ttauuttuuu uauttuauag aagggaagay guuttuagag agatgautua 240tygguuaggt uuuatggtgg ggutgauuuy gtuyggttgg ttuuaguaut utuagaguuu 300229300DNAArtificial SequenceSynthetic polynucleotide 229guyguygutt ttuuagtutt guuuaauuyg gtatttutgy guttguutua guuauuygua 60ggagyguagg uyguuuttyg tuutuuygtu ututgyguuu auaggauuuy ggguuuyguu 120uagtuyguag gtuuyguagg tuuuuuyggg ygtgtuttuu tgguuutgyg auuuuyggga 180uagygutgag aauaygygga aggtggggag aygygyggyg utgguygggt uuutggyguy 240gttutygygg tguaguutgt guutgggagt uygguygtuu uauutuagaa uuagaguaaa 300230300DNAArtificial SequenceSynthetic polynucleotide 230tttgututgg ttutgaggtg ggaygguygg autuuuaggu auaggutgua uygygagaay 60ggyguuaggg auuygguuag yguygygygt utuuuuauut tuygygtgtt utuagygutg 120tuuygggggt yguaggguua ggaagauayg uuygggggga uutgygggau utgyggautg 180ggygggguuy ggggtuutgt gggyguagag gaygggagga ygaagggygg uutgygutuu 240tgygggtggu tgagguaagy guagaaatau ygggttgggu aagautggaa aagyggyggu 300231300DNAArtificial SequenceSynthetic polynucleotide 231uutgggauag gutuaatgga ggutguaggg uuatuaguyg autuutaygu aggutuagtu 60aguaguuuuu tgguuaguuu uauuuutgau tguygguutu agaautggga gutguttuut 120gguaggguuy guututgutg ggagauygga yggtgagtua guuttaaguu ygguauuaga 180uuuututgag gatggaguag gagutggutg uuutgaggut guaaaauttu ttuuutygtg 240gagauaggga gguauutuag auautuauuu yggautuuut tgaauaggga uagggaggaa 300232300DNAArtificial SequenceSynthetic polynucleotide 232ttuutuuutg tuuutgttua agggagtuyg gggtgagtgt utgaggtguu tuuutgtutu 60uaygagggaa gaagttttgu aguutuaggg uaguuagutu utgutuuatu utuagagggg 120tutggtguyg gguttaaggu tgautuauyg tuyggtutuu uaguagaggy ggguuutguu 180aggaaguagu tuuuagttut gagguyggua gtuaggggtg gggutgguua gggggutgut 240gautgaguut gygtaggagt yggutgatgg uuutguaguu tuuattgagu utgtuuuagg 300233300DNAArtificial SequenceSynthetic polynucleotide 233auautgtggg guagggaggg guatututtg agaauaaaag atuuatttut ygautttuua 60aautggagag uttuttgaga gaaaagagag agauaggtau aggtuuaygu uauuuauaua 120uaguuutgtg uauauagauy ggauauaggy gtuuauaggu aagttyguag utgutuattt 180tgtgaagtga atgutgattt ggggguyggg tggggttygt utgtauatyg tguautgtua 240gauuuttuut gaaggatttt tgttautgaa gtatuagaag guuuttgttu taaggtggtg 300234300DNAArtificial SequenceSynthetic polynucleotide 234auuauuttag aauaaggguu ttutgataut tuagtaauaa aaatuuttua ggaagggtut 60gauagtguay gatgtauaga ygaauuuuau uygguuuuua aatuaguatt uauttuauaa 120aatgaguagu tgygaauttg uutgtggayg uutgtgtuyg gtutgtgtgu auagggutgt 180gtgtgggtgg ygtggauutg tauutgtutu tututtttut utuaagaagu tutuuagttt 240ggaaagtyga gaaatggatu ttttgttutu aagagatguu uutuuutguu uuauagtgtg 300235300DNAArtificial SequenceSynthetic polynucleotide 235auuuaygggg auaggggtua gagtaatgga gtggaaatgg uaggttuaua attttgguta 60uagutgutuu uatututaag uaauuuaggu tuygggttgg agggtggyga uuuuaagatg 120ygguutuagu yguygguygt gtttgtgutu uaguygatga agygagtgua aagggutgta 180uaaaygygag guautgaaua aauautgagy gtguygtuua gatgtuuygg gggaggutga 240ggatuuauau ygtggggagt gututguuuu uatggagtga uutggygtuy guuutuuayg 300236300DNAArtificial SequenceSynthetic polynucleotide 236ygtggagggy ggayguuagg tuautuuatg gggguagagu autuuuuayg gtgtggatuu 60tuaguutuuu uygggauatu tggaygguay gutuagtgtt tgttuagtgu utygygtttg 120tauaguuutt tguautygut tuatyggutg gaguauaaau aygguyggyg gutgagguyg 180uatuttgggg tyguuauuut uuaauuygga guutgggttg uttagagatg ggaguagutg 240taguuaaaat tgtgaauutg uuatttuuau tuuattautu tgauuuutgt uuuygtgggt 300237300DNAArtificial SequenceSynthetic polynucleotide 237ygaggtgygg utguuuygyg guttuutygg uttuuygtuu ygygtguttt uutggagtuu 60utuuttuygg agguuutuut guutuuaygt gtguuuttut uuatgtuuag uattygggyg 120uututtgtut ttuttutgtt uuutggutty ggygtuuuyg ggagtgtgau tuuyguagyg 180gggtguagut ttuututggg atgagtgauy ggagggaauu yguuttuuyg gguaygtygu 240uaguututtu ututtuttuu utaggutatu aagyggautt atgauaagaa ggyggtggat 300238300DNAArtificial SequenceSynthetic polynucleotide 238atuuauyguu ttuttgtuat aagtuygutt gataguutag ggaagaagag gaagaggutg 60gygaygtguu ygggaaggyg ggttuuutuy ggtuautuat uuuagaggaa agutguauuu 120ygutgyggga gtuauautuu yggggayguy gaaguuaggg aauagaagaa agauaagagg 180yguuygaatg utggauatgg agaaggguau aygtggaggu aggaggguut uyggaaggag 240ggautuuagg aaaguaygyg ggaygggaag uygaggaagu ygygggguag uyguauutyg 300239300DNAArtificial SequenceSynthetic polynucleotide 239tguagtgtgt auaggautuu utgaaagggu tuuutgggat ggaggguttt tggggggguu 60tgtggttutt utuuaguatg agtuauaaau uauatuutuu auagtuaguy ggatuuaaau 120ygatttgauy gagatyggut uttuaatgyg gtutuuyggg gtgtuuuyga ggatutggut 180ggauttuuag agtauutgag uaagauuagu aagtauutua uygautygga atauauaggt 240agauuutguu utgtggatuu aaggutaggu atuutgtgag utgatagtta ggtgggutgt 300240300DNAArtificial SequenceSynthetic polynucleotide 240uaguuuauut aautatuagu tuauaggatg uutaguuttg gatuuauagg guagggtuta 60uutgtgtatt uygagtyggt gaggtauttg utggtuttgu tuaggtautu tggaagtuua 120guuagatuut yggggauauu uygggagauy guattgaaga guygatutyg gtuaaatygg 180tttggatuyg gutgautgtg gaggatgtgg tttgtgautu atgutggaga agaauuauag 240guuuuuuuaa aaguuutuua tuuuagggag uuutttuagg gagtuutgta uauautguau 300241300DNAArtificial SequenceSynthetic polynucleotide 241aggaguutgt gauuuagaaa tggtaagtaa ggtuygattu tuauuaauaa aguagguatg 60auutuagaua agtuuutauu utgututggg uutuagtttu tuutttagtg aggaggtggg 120tgagggtuut gtuutuutuy gggaautggy gatttgggaa gguagagaua ttuuuagaat 180uyguyggagt uutgaaaaua uuuayguuut ttgtuuuagu aatuutgaga aagguuauau 240tgataaagut gtgggtgguu agatgauagu attuttgggu utuagaygaa gtgggagggg 300242300DNAArtificial SequenceSynthetic polynucleotide 242uuutuuuaut tygtutgagg uuuaagaatg utgtuatutg guuauuuaua gutttatuag 60tgtgguuttt utuaggattg utgggauaaa gggygtgggt gttttuagga utuyggygga 120ttutgggaat gtututguut tuuuaaatyg uuagttuuyg gaggaggaua ggauuutuau 180uuauutuutu autaaaggag aaautgaggu uuagaguagg gtagggautt gtutgaggtu 240atguutgutt tgttggtgag aatyggauut tauttauuat ttutgggtua uaggutuutt 300243300DNAArtificial SequenceSynthetic polynucleotide 243aguuutggut gagtguuuuu uauttuuutg gutygagttu uutgaggaaa aaaggtggtg 60autuutuutg uauagaauaa aggutgagtg agguauagtg uuuaggggat gaggaaggut 120gaguuyggga uuagguagga ggaauutguy gtguautuau tuagautuut guaguauuyg 180ggguaggtgu tuuauuagyg gguauaguyg utuaguyguu tuutuatuuy guyguaguua 240gtggatuauu auagutgtua gagagguuua uuauttgguu auygggtuta yguutguaga 300244300DNAArtificial SequenceSynthetic polynucleotide 244tutguaggyg tagauuyggt gguuaagtgg tggguututu tgauagutgt ggtgatuuau 60tggutgyggy gggatgagga ggyggutgag yggutgtguu ygutggtgga guauutguuu 120ygggtgutgu aggagtutga gtgagtguay gguaggttuu tuutguutgg tuuygggutu 180aguuttuutu atuuuutggg uautgtguut uautuaguut ttgttutgtg uaggaggagt 240uauuauuttt tttuutuagg gaautygagu uagggaagtg ggggguautu aguuagggut 300245300DNAArtificial SequenceSynthetic polynucleotide 245ututgggutu tutuuauagg gttgagguua gagutattut uagaatuuyg uyggaggggu 60uttguutgga ggaggguaua aygauautta uttgtuuuua tuagutgauu uagggutggg 120gttgggutgg gtuauauagt tuagtgutyg ututaagaga tgttuuygga atagutgagt 180uauutggguu agggggtuua utgtggagag gaggaggtga gtggggtggg gaguaggguu 240uuauuutuut utuuaaguta aggguttttt uutgggtggg utgggguuau auutaggguu 300246300DNAArtificial SequenceSynthetic polynucleotide 246guuutaggtg tgguuuuagu uuauuuagga aaaaguuutt aguttggaga ggagggtggg 60guuutgutuu uuauuuuaut uauutuutuu tutuuauagt ggauuuuutg guuuaggtga 120utuagutatt uygggaauat ututtagagy gaguautgaa utgtgtgauu uaguuuaauu 180uuaguuutgg gtuagutgat ggggauaagt aagtgtygtt gtguuutuut uuagguaagg 240uuuutuyggy gggattutga gaatagutut gguutuaauu utgtggagag aguuuagagu 300247300DNAArtificial SequenceSynthetic polynucleotide 247yguuutggut utgggutttu auuauyguut gggguuutgu ttggaututg uagutgtgtu 60uuaaggutgy guuutagatt tgtutautuu ttuuuutguu uuutuuutgu tttutuuygg 120uututgtagt uttuutgutu utuuauutay gtggutguut tggguuuuat guagutuutu 180uuuygggatg uuuuatgutu tgttutgtga utguuttaut uttgatuauu tutgatggut 240gutuuagtgu agguagaauu uuuaaagtuu tutgttutut auatgtuuuu utttguuauu 300248300DNAArtificial SequenceSynthetic polynucleotide 248ggtgguaaag ggggauatgt agagaauaga ggautttggg ggttutguut guautggagu 60aguuatuaga ggtgatuaag agtaagguag tuauagaaua gaguatgggg uatuuygggg 120gaggagutgu atgggguuua agguaguuay gtaggtggag gaguaggaag autauagagg 180uygggagaaa guagggaggg gguaggggaa ggagtagaua aatutagggy guaguuttgg 240gauauagutg uagagtuuaa guaggguuuu aggyggtggt gaaaguuuag aguuagggyg 300249300DNAArtificial SequenceSynthetic polynucleotide 249tttuutuutu tutttuuttu uttutuuagt tuutuuuttt tuutuuttua utgtttgatt 60tttaguuutu tgattttttu ttuututtut uuaututtta tttuttttua tuutuutuuy 120ggtuuttttt tutgutttgt uauutuutty gttttuttut utututggut gautuagggg 180auyggaggtg gguutatutg gagtgagtga gtaagtgtgt tgggaggtga gggtggaggg 240utggaggggg guagtgatut gguutgaguu uutuuagtat tgutuuaguu uuaguyguag 300250300DNAArtificial SequenceSynthetic polynucleotide 250utgyggutgg ggutggagua atautggagg ggutuagguu agatuautgu uuuuutuuag 60uuutuuauuu tuauutuuua auauauttau tuautuautu uagatagguu uauutuyggt 120uuuutgagtu aguuagagag agaagaaaay gaaggaggtg auaaaguaga aaaaaggauy 180gggaggagga

tgaaaagaaa taaagagtgg agaagaggaa gaaaaaatua gagggutaaa 240aatuaaauag tgaaggagga aaagggagga autggagaag gaaggaaaga gaggaggaaa 300251300DNAArtificial SequenceSynthetic polynucleotide 251utataututu agguuuaggu uaggggyggu agutguuuuu utuautguuu uayguauaaa 60tuuutggttt uagtuuaaau ygutautgtg agutuuagat utgggtgggg uuyggaguut 120uutuattagu auuaggtggg atgguuttgy gaagataaag ututgtutgg uuuuaguuua 180ggutgtaguu uyggguuutg uuuuagguag uutguuuagg atgutgtguu agtttutgau 240utttguuuau tguaguuaga tgggguuatu tgtggagutg guuttttutu uttagaatga 300252300DNAArtificial SequenceSynthetic polynucleotide 252tuattutaag gagaaaaggu uagutuuaua gatgguuuua tutggutgua gtggguaaag 60gtuagaaaut gguauaguat uutggguagg utguutgggg uaggguuygg ggutauaguu 120tgggutgggg uuagauagag utttatutty guaagguuat uuuauutggt gutaatgagg 180aggutuyggg uuuuauuuag atutggagut uauagtagyg gtttggautg aaauuaggga 240tttgtgygtg ggguagtgag ggggguagut guyguuuutg guutggguut gagagtatag 300253300DNAArtificial SequenceSynthetic polynucleotide 253aygggtgtut gutuuuaagu tggguauuuu tuuuuuaggu tgtgggaauy gutggguuat 60tutgauutyg aauuagaaat aguuuygauu uuuututttu tuuuygyguu uuuaguygga 120uyguuuuuyg ggauuuuagu uaaauuauag ygtuygguat aggguututu uuttattgua 180uaauygutag gggagauaga gaggatgggg gtuuygggaa uatgutgggg tyguuagaut 240atgggaygta ggggygtagu tuauutgttg gagauagguu ygutuutuau tggutgagtu 300254300DNAArtificial SequenceSynthetic polynucleotide 254gautuaguua gtgaggagyg gguutgtutu uaauaggtga gutayguuuu taygtuuuat 60agtutggyga uuuuaguatg ttuuygggau uuuuatuutu tutgtutuuu utagyggttg 120tguaataagg gagagguuut atguyggayg utgtggtttg gutggggtuu yggggggygg 180tuyggutggg ggygygggga gaaagagggg ggtyggggut atttutggtt ygaggtuaga 240atgguuuagy ggttuuuaua guutggggga ggggtguuua guttgggagu agauauuygt 300255300DNAArtificial SequenceSynthetic polynucleotide 255guagtaaaua gtuutattgt auaaatatat agygygggut gggygggggy ggtuaauuuy 60ggttuuutgg uayggggaua gggygygutg gguuyggutu tguagygagu yggtgggagg 120guutagutgt gguuuaggyg gtgttgagua yggguygggg gygtuatagu yggggagggu 180yggguagyga gygggtgggy gaggggygag tuatygtutg uuuyguuygg aggggauuuy 240ggygggtgag ggaygtgggt ggagggagay gtggggagut uagtyggagt agatgatgaa 300256300DNAArtificial SequenceSynthetic polynucleotide 256ttuatuatut autuygautg agutuuuuay gtutuuutuu auuuaygtuu utuauuyguy 60ggggtuuuut uygggygggg uagaygatga utyguuuuty guuuauuygu tygutguuyg 120guuutuuuyg gutatgaygu uuuygguuyg tgutuaauau yguutggguu auagutaggu 180uutuuuauyg gutygutgua gaguyggguu uagygyguuu tgtuuuygtg uuagggaauy 240ggggttgauy guuuuyguuu aguuygygut atatatttgt auaataggau tgtttautgu 300257300DNAArtificial SequenceSynthetic polynucleotide 257agttatttaa tauatgguuu uagtgguaut aauutgtuau taaguutuat gttutuuatu 60uataaaatgg agauuauaat uatauutgut guaaaatuua aaattuagag gtttutauag 120ygtgauygau autgtguuuy ggagagttty gguuututuu tggututggu uuuutggaau 180aygtgatguu uaguuuaaau agtguuauau uutgututau aatguutuaa ygagagtuau 240aauuaaagat ttttgagtua gaggauaata gaggaggtgg gaautgggta aayggagagt 300258300DNAArtificial SequenceSynthetic polynucleotide 258ututuygttt auuuagttuu uauutuutut attgtuutut gautuaaaaa tutttggttg 60tgaututygt tgagguattg tagaguaggg tgtgguautg tttgggutgg guatuaygtg 120ttuuaggggg uuagaguuag gagaggguyg aaaututuyg ggguauagtg tyggtuaygu 180tgtagaaauu tutgaatttt ggattttgua guaggtatga ttgtggtutu uattttatgg 240atggagaaua tgagguttag tgauaggtta gtguuautgg gguuatgtat taaataautg 300259300DNAArtificial SequenceSynthetic polynucleotide 259gagtttyggu uututuutgg ututgguuuu utggaauayg tgatguuuag uuuaaauagt 60guuauauuut gututauaat guutuaayga gagtuauaau uaaagatttt tgagtuagag 120gauaatagag gaggtgggaa utgggtaaay ggagagtuua tgguutttgg aggtggggua 180uaguuyggag tgaatgaggg uuuagagttt uuagagaauy gaatatagat utgtgtgtga 240aguutuuaga tattutaatg ttgauaayga aatuaaattg aaaaaaaata aaaatuaata 300260300DNAArtificial SequenceSynthetic polynucleotide 260attgattttt attttttttu aatttgattt ygttgtuaau attagaatat utggaggutt 60uauauauaga tutatattyg gttututgga aaututgggu uutuattuau tuygggutgt 120guuuuauutu uaaagguuat ggaututuyg tttauuuagt tuuuauutuu tutattgtuu 180tutgautuaa aaatutttgg ttgtgautut ygttgaggua ttgtagagua gggtgtggua 240utgtttgggu tggguatuay gtgttuuagg ggguuagagu uaggagaggg uygaaautut 300261300DNAArtificial SequenceSynthetic polynucleotide 261ygggtgygga uuyguuauut guyguauuut tuuuttuuua auuutguuut ttuuuuauuu 60uuauuuuaut tuuuauuuuu aauuuuygut yggyguuuua utuuygauuu tguutguuyg 120gguauutygg ggygtuygut yguyggutty guutuuautt guuuygguag gygygygtgg 180gutyggygtu uygygutuuu tuutygautg tgyggutuuy gygutguygg gtttuutgtt 240uaauaatata auuagggagg uauyggygga gagyguyggg uagaauttuu tuuyggautg 300262300DNAArtificial SequenceSynthetic polynucleotide 262uagtuyggga ggaagttutg uuyggygutu tuyguyggtg uutuuutggt tatattgttg 60aauaggaaau uygguagygy gggaguygua uagtygagga gggagygygg gayguygagu 120uuaygygygu utguyggggu aagtggaggy gaaguyggyg agyggayguu uygaggtguu 180yggguaggua gggtygggag tggggyguyg agygggggtt gggggtggga agtggggtgg 240gggtggggaa aggguagggt tgggaaggga agggtgyggu aggtggyggg tuyguauuyg 300263300DNAArtificial SequenceSynthetic polynucleotide 263gguaagguag tutgggyguy gtutuyggtu tygggguutg yggtyggggu auygyggtgu 60ygygtttgag uyggtuagut uuutgyggaa attauagggg ygutyggygu tgyggtygyg 120uuuuuygggg uagyguuygu tggttggagg ygtttaaatt gaaaguagut ttggggagag 180ggggyggayg yggguyguyg aguaagggga gggggygguu ygguauagyg auuuuattgt 240utgtguuygu ygaggggtgg aauuttgygg tgagutyggy gyggyguuuu utuuuygagu 300264300DNAArtificial SequenceSynthetic polynucleotide 264gutyggggag ggggyguygy guygagutua uyguaaggtt uuauuuutyg gyggguauag 60auaatggggt ygutgtguyg gguyguuuuu tuuuuttgut yggygguuyg ygtuyguuuu 120ututuuuuaa agutgutttu aatttaaayg uutuuaauua gygggygutg uuuygggggg 180ygygauygua gyguygagyg uuuutgtaat ttuyguaggg agutgauygg utuaaaygyg 240guauygyggt guuuygauyg uagguuuyga gauyggagay ggyguuuaga utguuttguu 300265300DNAArtificial SequenceSynthetic polynucleotide 265ggagggaguu tguaututgg guagtgatgt ggagtuagag atttuuaagt tuatggtgua 60agtutgtggg agaguagaau tuautttaua aaattgttga uaguyggtgt tgttagagay 120ggaaagggau aauuuyggut uututuuagg ygtggagtut gtggggatgt guttuuagaa 180aatguagggt taaguaggag utguagagta gaatuaaatg auaatgautu autgutgtua 240utaauaggut utttgtgggg gutgtaggtg ggaggygata tgguygguau uttyguauaa 300266300DNAArtificial SequenceSynthetic polynucleotide 266ttgtgygaag gtguygguua tatyguutuu uauutauagu uuuuauaaag aguutgttag 60tgauaguagt gagtuattgt uatttgattu taututguag utuutgutta auuutguatt 120ttutggaagu auatuuuuau agautuuayg uutggagagg aguyggggtt gtuuutttuy 180gtututaaua auauyggutg tuaauaattt tgtaaagtga gttutgutut uuuauagaut 240tguauuatga auttggaaat ututgautuu auatuautgu uuagagtgua ggutuuutuu 300267300DNAArtificial SequenceSynthetic polynucleotide 267gttutggtty gguagagtgg ygguaatutt guutututut utagaauauu taaagaaguu 60agtgagtgag utgutuatgu auauygggga gauutauaga yggatuuagg aggagyggga 120gutuattgau tguauauttu uaauuyggyg tgataggaaa gtgagguuau utgtuutaag 180tguuyggggg uaggggggtu uatggaggag ggggyggggg uaggtgtutg gauauaggga 240tgutggtutu aggtgguaua gutggggaga aaaaauutat uuattguaaa auatuattag 300268300DNAArtificial SequenceSynthetic polynucleotide 268taatgatgtt ttguaatgga taggtttttt utuuuuagut gtguuauutg agauuaguat 60uuutgtgtuu agauauutgu uuuyguuuuu tuutuuatgg auuuuuutgu uuuyggguau 120ttaggauagg tgguutuaut ttuutatuay guygggttgg aagtgtguag tuaatgagut 180uuygutuutu utggatuygt utgtaggtut uuuyggtgtg uatgaguagu tuautuautg 240guttutttag gtgttutaga gagagaggua agattguygu uaututguyg aauuagaaua 300269300DNAArtificial SequenceSynthetic polynucleotide 269ygtgatuaga gauagaaatu agutuuuutu utuuutuaut gaguttgtag uuautttaag 60tataauutgt gtuutgtguu agttuuauua taaatuaguu utgagttuta tuyggyggut 120tattutgutg uuaaaauutt uattagttgy gggaatgggu uagggagaga guuyggautt 180tautuyggut gtggtgautu ayguutttgg gaagggutga ggtatttgtu uttggatgtg 240gggatgutgt gguututggt tgggaauaua guutygtttt gtutgutggu tutgguttuu 300270300DNAArtificial SequenceSynthetic polynucleotide 270ggaaguuaga guuaguagau aaaaygaggu tgtgttuuua auuagagguu auaguatuuu 60uauatuuaag gauaaatauu tuaguuuttu uuaaaggygt gagtuauuau aguyggagta 120aagtuygggu tututuuutg guuuattuuy guaautaatg aaggttttgg uaguagaata 180aguyguygga tagaautuag ggutgattta tggtggaaut gguauaggau auaggttata 240uttaaagtgg utauaagutu agtgagggag gaggggagut gatttutgtu tutgatuayg 300271300DNAArtificial SequenceSynthetic polynucleotide 271uagtatguat gtgtuuattt aagguatutg aguuutgguu tttgutgttu ttuuttuutt 60utttutuygt ygggttgutg agutuaauat uuuauygggu tuutgutuut tagutaguag 120tuagtguaga gutgutgggt uuttutguut yguttgggua gguttutgtu aatgagtuau 180uaaguauygg gaaataagtg uauaggaagg aguaggtggu aagauuutgt ggaggtagag 240auagttuuat tuagtgagtg agutgtgaut guaaatttgg gaaggttutg ggggaaguaa 300272300DNAArtificial SequenceSynthetic polynucleotide 272ttguttuuuu uagaauuttu uuaaatttgu agtuauagut uautuautga atggaautgt 60ututauutuu auagggtutt guuauutgut uuttuutgtg uauttatttu uyggtguttg 120gtgautuatt gauagaaguu tguuuaagyg agguagaagg auuuaguagu tutguautga 180utgutaguta aggaguagga guuyggtggg atgttgagut uaguaauuyg ayggagaaag 240aaggaaggaa gaauaguaaa gguuagggut uagatguutt aaatggauau atguatautg 300273300DNAArtificial SequenceSynthetic polynucleotide 273ygguygyggg gggyguutgg aggagggaag uututuygga ggagaagagu tgggygguyg 60uygtaggagg aagyggaaag ataagggguu utyggutygg ygggguyguy ggayguuuag 120gaguutuaat ggggauaygt ygggtgggga yggagguagu tuutgtuygg auagygaaau 180uygygagguu uaggagagyg guaguuagyg ygguauaguu ygggagutgy gguuuayguy 240ggaguutayg gauatgggut yggaagggau aaaaauyggg uyggagtuag ygutggaguu 300274300DNAArtificial SequenceSynthetic polynucleotide 274ggutuuagyg utgautuygg uuyggttttt gtuuuttuyg aguuuatgtu ygtaggutuy 60ggygtggguy guagutuuyg ggutgtguyg ygutggutgu ygututuutg gguutygygg 120gtttygutgt uyggauagga gutguutuyg tuuuuauuyg aygtgtuuuu attgaggutu 180utgggygtuy ggygguuuyg uygaguygag gguuuuttat utttuygutt uutuutaygg 240ygguyguuua gututtutuu tuyggagagg uttuuutuut uuaggyguuu uuygygguyg 300275300DNAArtificial SequenceSynthetic polynucleotide 275guatuauaua tuuutuuutg tutuuutgut guuaauuagt tuuauuautg tguauututg 60uuuuaattuu auutuuuayg uutgutgutg uauuttggau ttgttttuut gaaattguat 120guuatuuaut utuuuttuta uttutgutgy gtuuututtg uuutatuagg auutgtggau 180tuaggautuu ygggutttut uuuuuatutu tuttuuuygt tggguutuau tauuatttua 240guuautttuu tgguaguttu autuutguuu uaagauuuua guutuuauuu tuutggttut 300276300DNAArtificial SequenceSynthetic polynucleotide 276agaauuagga gggtggaggu tggggtuttg ggguaggagt gaagutguua ggaaagtggu 60tgaaatggta gtgagguuua ayggggaaga gagatggggg agaaaguuyg ggagtuutga 120gtuuauaggt uutgataggg uaagagggay guaguagaag tagaagggag agtggatggu 180atguaatttu aggaaaauaa gtuuaaggtg uaguaguagg ygtgggaggt ggaattgggg 240uagaggtgua uagtggtgga autggttggu aguagggaga uagggaggga tgtgtgatgu 300277300DNAArtificial SequenceSynthetic polynucleotide 277ggtggygatg ututaguuau utguttutut gtuututttu auauaaatgt atuutguttu 60tttuuagatg tuygguttaa tgggautgga tttatuttua aaagtuutgg tttguututg 120attgaaaauu agtgtgutuu uuatggttay ggayggutgt guaggttttt gttttgttga 180agggaattgg utuaututga gtuaguygtg uauuygggut gutgatgtag tutuagtgtg 240atggttaaau tttaagtgtu aatttgautg ggutaaggaa tguuagauat tatttuyggg 300278300DNAArtificial SequenceSynthetic polynucleotide 278uuyggaaata atgtutggua ttuuttaguu uagtuaaatt gauauttaaa gtttaauuat 60uauautgaga utauatuagu aguuygggtg uayggutgau tuagagtgag uuaattuuut 120tuaauaaaau aaaaauutgu auaguygtuy gtaauuatgg ggaguauaut ggttttuaat 180uagagguaaa uuaggauttt tgaagataaa tuuagtuuua ttaaguygga uatutggaaa 240gaaguaggat auatttgtgt gaaagaggau agagaaguag gtggutagag uatyguuauu 300279300DNAArtificial SequenceSynthetic polynucleotide 279ggttttgggt gtggauatuu tggagggutg ttttagtguu uauauuaatg uuutagttaa 60agaauuauuu tgtuuuutta guuttutgua ggauaggtgg gaaaggguyg ggtgtutggt 120uutgutguua ggggauagtg uaggtgtgau ygtuygggua gagatgagtu auuutuuaua 180utgtuttgut guuygtutuu ayguutagtt ttagutygtg tggtuaagaa ggggygattu 240utuauutaga auauatgggt uauaaatgut auutttgaaa atggaaauaa aaataauuua 300280300DNAArtificial SequenceSynthetic polynucleotide 280tgggttattt ttgtttuuat tttuaaaggt aguatttgtg auuuatgtgt tutaggtgag 60gaatyguuuu ttuttgauua uaygagutaa aautaggygt ggagaygggu aguaagauag 120tgtggagggt gautuatutu tguuyggayg gtuauauutg uautgtuuuu tgguaguagg 180auuagauauu ygguuutttu uuauutgtuu tguagaaggu taaggggaua gggtggttut 240ttaautaggg uattggtgtg gguautaaaa uaguuutuua ggatgtuuau auuuaaaauu 300281300DNAArtificial SequenceSynthetic polynucleotide 281uagaauutga gygatgaagt gaygggattt agtuagguut atgaagagtu aatgguautt 60guutuuuata atuuttuuag tuuuattggu uaauuygtut gtuuutygyg tgatuttttt 120ggatutgaag tggtgtttua ggauuyggag ygtgguutgu autguuttgt tutgtttgtt 180tgtguauygg attuatygtg autuatuutg agtuatuuag guagtatgga agaautttgg 240agttatttta aauuutttgg utuagaauuu uatttuttut agaattaaua tguaagataa 300282300DNAArtificial SequenceSynthetic polynucleotide 282ttatuttgua tgttaattut agaagaaatg gggttutgag uuaaagggtt taaaataaut 60uuaaagttut tuuatautgu utggatgaut uaggatgagt uaygatgaat uyggtguaua 120aauaaauaga auaagguagt guagguuayg utuygggtuu tgaaauauua uttuagatuu 180aaaaagatua ygygagggau agaygggttg guuaatggga utggaaggat tatgggaggu 240aagtguuatt gaututtuat agguutgaut aaatuuygtu auttuatygu tuaggttutg 300283300DNAArtificial SequenceSynthetic polynucleotide 283gtuuuttggu auuaggauat uauuutuuua uututuuuag auuuttutuu ttgauututt 60tagaguaguu atuuttggag ttgutuaayg uuututtutu ttutuuutut gaauuauagu 120ttggutuatu tauttuyggg ttagutuaay guuututtut tttutuuutu tgaauuauag 180uttggutuat utauttuygg gttagutuaa yguaututtu tuttutuuut utgaauuayg 240guttggutua tutauttutg ggttaattta ggutttutuu auagatagtu tgaaaaggga 300284300DNAArtificial SequenceSynthetic polynucleotide 284tuuuttttua gautatutgt ggagaaaguu taaattaauu uagaagtaga tgaguuaagu 60ygtggttuag agggagaaga gaagagtgyg ttgagutaau uyggaagtag atgaguuaag 120utgtggttua gagggagaaa agaagagggy gttgagutaa uuyggaagta gatgaguuaa 180gutgtggttu agagggagaa gagaagaggg ygttgaguaa utuuaaggat ggutgututa 240aagaggtuaa ggagaagggt utgggagagg tgggagggtg atgtuutggt guuaagggau 300285300DNAArtificial SequenceSynthetic polynucleotide 285utgagtuaau aaggutgaua aggutgtgtt utggatguag guuygguaga tgtttgaggg 60ggaggtgguu aguutggagg uuutuaggag uayggguutg gtgygggtgu ygagguuuat 120gaaggtuaty gauutguygg gaggtggggu yguutttgtg atggaguatt tgaagatgaa 180gaguttgagu aggtgagtgt gtgtgagauu uatatgygua uatgtgtaua gguagagaga 240gautuagaga uaaauagaga gagauagaga aagggataga gatggggagg gagauagaaa 300286300DNAArtificial SequenceSynthetic polynucleotide 286tttutgtutu uutuuuuatu tutatuuutt tututgtutu tututgtttg tututgagtu 60tutututguu tgtauauatg tgyguatatg ggtutuauau auautuauut gutuaagutu 120ttuatuttua aatgutuuat uauaaaggyg guuuuauutu uygguaggty gatgauuttu 180atggguutyg guauuyguau uagguuygtg utuutgaggg uutuuaggut gguuauutuu 240uuutuaaaua tutguygggu utguatuuag aauauaguut tgtuaguutt gttgautuag 300287300DNAArtificial SequenceSynthetic polynucleotide 287ttygtguaut utgygguygy ggygguagua guygyggygg ygguuagutu uuyggtutay 60gtguuuauua uuygygtggg ttuuatgutg uuygguutau ygtauuauut guaggggtyg 120gguagtgggu uaguuaauua ygygggyggy gygggygygu auuuyggutg guutuagguu 180tygguygaua guuutuuata ygguagygga ggyggygygg utggyggygg gguygygggg 240uutggyggyg utggutuagu ygyggyguay gtutyggygy guttuuuuta ututuuuagu 300288300DNAArtificial SequenceSynthetic polynucleotide 288gutgggagag taggggaagy gyguygagay gtgyguygyg gutgaguuag yguyguuagg 60uuuygygguu uyguyguuag uygyguyguu tuygutguyg tatggagggu tgtygguyga 120gguutgaggu uaguyggggt gygyguuygy guyguuygyg tggttggutg guuuautguu 180ygauuuutgu aggtggtayg gtagguyggg uaguatggaa uuuaygyggg tggtggguay 240gtagauyggg gagutgguyg uyguygyggu tgutguyguy gygguyguag agtguaygaa 300289300DNAArtificial SequenceSynthetic polynucleotide 289tutttgtgtg agtuatgtut tatatuuaau aagtautuaa aaaaagattt tttttttttt 60tttttaagat ggagtgtygu tutgtuauuu aggutggagt guagtgguat gatuttggut 120uautguaauu tutguutuuy gggttuaagy gattuttutg uutuaggutu utgagtagut 180ggaattauag guatguuuua uuauauuygg utaattttta tatgtaatag aaauaaggtt 240tuauuatgtt gguuagauag gtuttgaaut uutgauutua ggtgatuuau uuauutyggu 300290300DNAArtificial SequenceSynthetic polynucleotide 290guygaggtgg gtggatuauu tgaggtuagg agttuaagau utgtutgguu aauatggtga 60aauuttgttt utattauata taaaaattag uygggtgtgg tgggguatgu utgtaattuu 120agutautuag gaguutgagg uagaagaaty guttgaauuy gggagguaga ggttguagtg 180aguuaagatu atguuautgu autuuaguut gggtgauaga gygauautuu atuttaaaaa 240aaaaaaaaaa aaatuttttt ttgagtautt gttggatata agauatgaut uauauaaaga 300291300DNAArtificial SequenceSynthetic polynucleotide 291auuauuuuut gauuuutuat gautuauuua gutuutaagt guuuutgggu auuuagttut 60ttgtgguatg gguyggtgua agtttutata tgagaguuag agagauaggg agggagguuy 120gggutuutgg uuttttggga aaagatguuy gtutuagauu aguaaaagga gguagutgut 180ttaggaguuy gggaaaatgu uatuautgat agtattatta ttattttuuu attttuuutt 240tgtgttttta aaatgaaaag ttuagatuua tggggtaggg tagagtgggu utggagggag 300292300DNAArtificial SequenceSynthetic polynucleotide 292tuuutuuagg uuuaututau uutauuuuat ggatutgaau ttttuatttt aaaaauauaa 60agggaaaatg ggaaaataat aataatauta tuagtgatgg uattttuuyg ggutuutaaa 120guagutguut

uuttttgutg gtutgagayg gguatutttt uuuaaaaggu uaggaguuyg 180gguutuuutu uutgtututu tggututuat atagaaautt guauygguuu atguuauaaa 240gaautgggtg uuuaggggua uttaggagut gggtgagtua tgaggggtua gggggtggtt 300293300DNAArtificial SequenceSynthetic polynucleotide 293guaguaygua guuuuuaggg guuutaautu auuuuututt uuutuauagg guttuuutgu 60ygtuuagtgt tgggtgagaa aggtggaggg gauatgtagu uuyggatgga ggtguaguau 120uaaygagaga gutuygguut gtgggaggga ygutuaggut taggtuaaag uuaggagutu 180ygggaaauut gggttuaguy guuayguuuu ayggagggga uauauuuttu uutguutgat 240gguaggguuu atggtagaua aaauuuatga uutuauutut uutggutuua gggutuaguu 300294300DNAArtificial SequenceSynthetic polynucleotide 294ggutgaguuu tggaguuagg agaggtgagg tuatgggttt tgtutauuat ggguuutguu 60atuagguagg gaagggtgtg tuuuutuygt ggggygtggy ggutgaauuu aggtttuuyg 120gagutuutgg utttgauuta aguutgagyg tuuutuuuau agguyggagu tututygttg 180gtgutguauu tuuatuyggg gutauatgtu uuutuuauut ttutuauuua auautggayg 240guagggaagu uutgtgaggg aagagggggt gagttagggu uuutgggggu tgygtgutgu 300295300DNAArtificial SequenceSynthetic polynucleotide 295atttutttut auutgtuatt gaagtgaatu atuagtataa gtagygagut gggyguattu 60uttutuagtt gtgttaaaau ttgutggtat tuuuuyggta tuaguagagg tgtgtayggg 120uautguttta aaautgggaa ggaggaagay gagguuaggg aguyggaggg tuauuaaggt 180agatttuuag uagygutagt uuagutgaau autttuuagu uttgtttttu aguagutttg 240aggaaaagta taggtaagaa uaaagauauu autgtatgtt tgutatatga atguataaua 300296300DNAArtificial SequenceSynthetic polynucleotide 296gttatguatt uatataguaa auatauagtg gtgtutttgt tuttauutat auttttuutu 60aaagutgutg aaaaauaagg utggaaagtg ttuagutgga utagygutgu tggaaatuta 120uuttggtgau uutuyggutu uutgguutyg tuttuutuut tuuuagtttt aaaguagtgu 180uygtauauau ututgutgat auygggggaa tauuaguaag ttttaauaua autgagaagg 240aatgyguuua gutygutaut tatautgatg attuauttua atgauaggta gaaagaaatg 300297300DNAArtificial SequenceSynthetic polynucleotide 297attggtutgg tuututttut aauauutuuu auuygggatg uaguuaagag tggutguagu 60utaattttut auatgtaaau aatgauutua gtgatguuua ygggguuuut ututgguutt 120utuuuuutgg gaaaagautg agttutygay ggguatuuuu tuuuuutuyg gaauuaaggg 180ututgggatg ttgauaguuu uyguuauutu tgagaagggu agguygtgga aaauuatutu 240utuuuttuut tuuuuututg uutttuutag utgggguutu tguauaatgu agutggguua 300298300DNAArtificial SequenceSynthetic polynucleotide 298tgguuuagut guattgtgua gagguuuuag utaggaaagg uagaggggga aggaagggag 60gagatggttt tuuaygguut guuuttutua gaggtggygg gggutgtuaa uatuuuagag 120uuuttggttu yggaggggga ggggatguuy gtygagaaut uagtuttttu uuagggggag 180aagguuagag agggguuuyg tggguatuau tgaggtuatt gtttauatgt agaaaattag 240gutguaguua ututtggutg uatuuygggt gggaggtgtt agaaagagga uuagauuaat 300299300DNAArtificial SequenceSynthetic polynucleotide 299ttguuutuat utuuaggutt tggaggaggg taggtguutg guuaguagag tgguuautgu 60tuautgguuu agaggaagua agguuauuag uutgatuuua uttutuuutu ygguuuatut 120tuautuuuut utuutuaauu auaaguuuyg uuaaaataga gauuuuyggu tttgutuuuu 180tgutguagga agggagaguu auyguuagau autguutguu tggtuutuut gttutgatut 240uauuyggtgu ttggaatuaa agaggauutg guttuuutut ygggataygt gattttuttt 300300300DNAArtificial SequenceSynthetic polynucleotide 300aagaaaatua ygtatuuyga gagggaaguu aggtuututt tgattuuaag uauygggtga 60gatuagaaua ggaggauuag guagguagtg tutggyggtg gututuuutt uutguaguag 120gggaguaaag uygggggtut utattttggy gggguttgtg gttgaggaga ggggagtgaa 180gatggguygg agggagaagt gggatuaggu tggtgguutt guttuututg gguuagtgag 240uagtgguuau tutgutgguu agguauutau uutuutuuaa aguutggaga tgaggguaag 300301300DNAArtificial SequenceSynthetic polynucleotide 301guuuagatua gguagygggg tyguuututu uaggaututu aagguaguta aggutggagg 60yguyggygag uutggagagg gaggagttua utaaattgtg ttggatggaa ggygtygagg 120auyggaggaa ttaatuygat gtggggaagg yggayggggu taygaggaaa aaagaggggg 180uaatgtauau tuaguutttt uatuautygg yggggagatg gatggttttu yggauygggy 240gtuuuagygu uuyggttagu tatagggaga ygtuagagyg ututggtuyg ygatagaaga 300302300DNAArtificial SequenceSynthetic polynucleotide 302tuttutatyg yggauuagag ygututgayg tutuuutata gutaauyggg gygutgggay 60guuyggtuyg gaaaauuatu uatutuuuyg uygagtgatg aaaaggutga gtgtauattg 120uuuuututtt tttuutygta guuuygtuyg uuttuuuuau atyggattaa ttuutuyggt 180uutygayguu ttuuatuuaa uauaatttag tgaautuutu uututuuagg utyguyggyg 240uutuuaguut tagutguutt gagagtuutg gagagggyga uuuygutguu tgatutgggu 300303300DNAArtificial SequenceSynthetic polynucleotide 303atttgguttg atuttatttt taatattttt tauautttut ututaaagaa aaaaaaggyg 60agtgaataty gtgatgggtg uagttatgut gaataattgg atgggaggay gtguuaggyg 120atutuuaguu uutgggaguy ggayguuuay guutuuutut guutygttut uauagauaua 180tttgtggggt gattaautua ggaattuatg utgutuaaag taautauagt ggtgagtgtt 240ttgauyggtt tgatgtagaa atuaaggaaa auauuagaaa aatuaggggy ggagguuuaa 300304300DNAArtificial SequenceSynthetic polynucleotide 304ttggguutuy guuuutgatt tttutggtgt tttuuttgat ttutauatua aauyggtuaa 60aauautuauu autgtagtta utttgaguag uatgaattuu tgagttaatu auuuuauaaa 120tgtgtutgtg agaaygaggu agagggaggy gtgggygtuy ggutuuuagg ggutggagat 180yguutgguay gtuutuuuat uuaattattu aguataautg uauuuatuay gatattuaut 240yguutttttt ttutttagag agaaagtgta aaaaatatta aaaataagat uaaguuaaat 300305300DNAArtificial SequenceSynthetic polynucleotide 305tgautttttu atttututua agatgatuat taggagtggt ttuaauaaaa utgaauauag 60aattttgagg guuuuaatua tgautuaauu agaguuutuu utgaattutt uatgagtuag 120uuygguuutu uuuautgaut tuauuutagy ggguauutgt utttuttutt uttttatuau 180tttttguttu tuttttggtt tuuagututg autgaattua gauuuaauau uttuuaattu 240ttuuygguuu uutuagggaa auuuagaggu aaatttgagt guagggagyg gggguttygu 300306300DNAArtificial SequenceSynthetic polynucleotide 306gygaaguuuu ygutuuutgu autuaaattt guututgggt ttuuutgagg ggguygggaa 60gaattggaag gtgttgggtu tgaattuagt uagagutgga aauuaaaaga gaaguaaaaa 120gtgataaaag aagaagaaag auaggtguuy gutagggtga agtuagtggg gaggguyggg 180utgautuatg aagaattuag ggagggutut ggttgagtua tgattggggu uutuaaaatt 240utgtgttuag ttttgttgaa auuautuuta atgatuatut tgagagaaat gaaaaagtua 300307300DNAArtificial SequenceSynthetic polynucleotide 307ggtgtuagga gtgguuuagg agaguauuuy gttuuuyggu uyguaggtgg tgtttgutgg 60utuuaguagg guuaggaggu uauutguagu utggtgutuu agautgatgt uauuyggguy 120gagtgutgtg uutuygguaa uattgauauy guutggtuua auutuauuua uuyggggaau 180aagatuaauu tuutyggutt uttggguutt gtuuautguu ttuuutguaa aggtgagauu 240tuagguuaga aguaggguag aygtutuagu tuaggauuag uuauaaauag tuatggtggt 300308300DNAArtificial SequenceSynthetic polynucleotide 308auuauuatga utgtttgtgg utggtuutga gutgagaygt utguuutgut tutgguutga 60ggtutuauut ttguagggaa gguagtggau aagguuuaag aaguygagga ggttgatutt 120gttuuuyggg tgggtgaggt tggauuaggy ggtgtuaatg ttguyggagg uauaguauty 180gguuygggtg auatuagtut ggaguauuag gutguaggtg guutuutggu uutgutggag 240uuaguaaaua uuauutgygg guyggggaay ggggtgutut uutggguuau tuutgauauu 300309300DNAArtificial SequenceSynthetic polynucleotide 309guaguuutut tuauutguut ggtgautuau tauaaguuut gggggaagga atgguagtgg 60uuututtuau utttautguu tutgygguua uaatggguag ttgauataau uauutguagg 120uuuygggagu uatygggguu tuttgauayg tgutuattag tgguttutga ggagyguutg 180uuuuauutgu uuuaygtguu uuuaygtutg guuautuuag ggtuuattag ygutaatygg 240uaaatguutg tgututuatu tauygggaaa auatutuuut tutuuagagy ggagguuagu 300310300DNAArtificial SequenceSynthetic polynucleotide 310utgguutuyg ututggagaa gggagatgtt ttuuyggtag atgagaguau agguatttgu 60ygattagygu taatggauuu tggagtgguu agaygtgggg guaygtgggg uaggtggggu 120aggygutuut uagaaguuau taatgaguay gtgtuaagag guuuygatgg utuuyggggu 180utguaggtgg ttatgtuaau tguuuattgt gguyguagag guagtaaagg tgaagagggu 240uautguuatt uuttuuuuua ggguttgtag tgagtuauua gguaggtgaa gagggutgut 300311300DNAArtificial SequenceSynthetic polynucleotide 311gtgguuutut tuauutttau tguututgyg guuauaatgg guagttgaua taauuauutg 60uagguuuygg gaguuatygg gguututtga uaygtgutua ttagtggutt utgaggagyg 120uutguuuuau utguuuuayg tguuuuuayg tutgguuaut uuagggtuua ttagygutaa 180tygguaaatg uutgtgutut uatutauygg gaaaauatut uuuttutuua gagyggaggu 240uaguutaaaa auuagguuyg uaguutuyga ggututgaaa auuaagyggu tgttutggtu 300312300DNAArtificial SequenceSynthetic polynucleotide 312auuagaauag uyguttggtt ttuagaguut yggaggutgy ggguutggtt tttaggutgg 60uutuygutut ggagaaggga gatgttttuu yggtagatga gaguauaggu atttguygat 120tagygutaat ggauuutgga gtgguuagay gtggggguay gtgggguagg tgggguaggy 180gutuutuaga aguuautaat gaguaygtgt uaagagguuu ygatggutuu ygggguutgu 240aggtggttat gtuaautguu uattgtgguy guagagguag taaaggtgaa gaggguuaut 300313300DNAArtificial SequenceSynthetic polynucleotide 313atggguuutg ggguyguygu utuagtgtut tutggtgutg uaguygggua ggguygaauu 60utggyguaua guttuutgut gagtutuuut ututaaggut gtutgtgggy ggututguyg 120guuuutuutg uauutguuua gguuutgggy ggaggutuut uutuuygggg gggutgtggu 180utuaguauag auuaggggau agaaggtggu tuttuttggu uttggutggg tgtgaauuaa 240agauttuutg taagaaatuu uuututuuut utuuutuutt ygutuuutua tutututuuu 300314300DNAArtificial SequenceSynthetic polynucleotide 314gggagagaga tgagggagyg aaggagggag agggagaggg ggatttutta uaggaagtut 60ttggttuaua uuuaguuaag guuaagaaga guuauuttut gtuuuutggt utgtgutgag 120guuauaguuu uuuygggagg aggaguutuy guuuaggguu tggguaggtg uaggaggggu 180ygguagaguy guuuauagau aguuttagag agggagautu aguaggaagu tgtgyguuag 240ggttygguuu tguuyggutg uaguauuaga agauautgag gyggygguuu uaggguuuat 300315300DNAArtificial SequenceSynthetic polynucleotide 315uautggauua tuuauauaau ttttgaggat uagtggaaat gaaaauaygg tguuuyggua 60uaaaauatat ttuatagutt gggttaggua auaguaaagu atuaygutga gyguygggau 120uttutgagtg uaggyggtgg gygaaguuuy gagtuauaua uauuuaygay guygguuutg 180utuuuauagy gguuututgg ggtagygaut ggtattauut guatttuayg agggaggaaa 240utgagguayg aautgttuag aagutguuut gaggtuauua agtgagutag gaagaggygt 300316300DNAArtificial SequenceSynthetic polynucleotide 316yguututtuu tagutuautt ggtgauutua ggguaguttu tgaauagtty gtguutuagt 60ttuutuuuty gtgaaatgua ggtaatauua gtygutauuu uagaggguyg utgtgggagu 120aggguyggyg tygtgggtgt gtgtgautyg ggguttyguu uauyguutgu autuagaagg 180tuuyggygut uagygtgatg utttgutgtt guutaauuua agutatgaaa tatgttttgt 240guygggguau ygtgttttua tttuuautga tuutuaaaag ttgtgtggat ggtuuagtgt 300317300DNAArtificial SequenceSynthetic polynucleotide 317utuuagtgtg uutuagttgg tttatutgta aaaatggggu uagguuayga utggtgttuu 60utttauagag aaguautuua gguaggggtg ggtgggggtg gaautygttu tuaatgguuu 120uygggauagu uutguaguua uyggtgauty gggttygtut gyggatuttt uuygguutuu 180autuuattua gggauaguuu tguaatgggg utuuutuuua aaaaaaygua tgguuttuut 240gtuuuuuaaa auuaguttaa ygguaguuat tuuutuuutu utuygggggu tgaaaaauua 300318300DNAArtificial SequenceSynthetic polynucleotide 318ggtttttuag uuuuyggagg agggagggaa tggutguygt taagutggtt ttgggggaua 60ggaagguuat gygttttttt gggagggagu uuuattguag ggutgtuuut gaatggagtg 120gagguyggga aagatuygua gaygaauuyg agtuauyggt ggutguaggg utgtuuyggg 180gguuattgag aaygagttuu auuuuuauuu auuuutguut ggagtguttu tutgtaaagg 240gaauauuagt ygtgguutgg uuuuattttt auagataaau uaautgaggu auautggagg 300319301DNAArtificial SequenceSynthetic polynucleotide 319uautuayggg utagutuygt uaggtgttga yggatgtuau tuaggtgtga gututguauu 60tgagutuuuu uutguauaua gguaguuaua auuagtuagt guagaggtga guutgtgguu 120agtgaggagu yggtgagtua auutuutuuy guutaygggu uutgagaygu yggutuygtg 180aguttgyggg gtygagggyg uutatattaa guuaaggutg agguagtgau auauuututt 240atggguutgu tutygutuuu tguttuattg tuutggtutu tuuututygt atggaggatu 300a 301320301DNAArtificial SequenceSynthetic polynucleotide 320tgatuutuua taygagaggg agagauuagg auaatgaagu agggagygag aguagguuua 60taagagggtg tgtuautguu tuaguuttgg uttaatatag gyguuutyga uuuyguaagu 120tuayggaguy ggygtutuag gguuygtagg ygggaggagg ttgautuauy ggutuutuau 180tgguuauagg utuauututg uautgautgg ttgtggutgu utgtgtguag gggggagutu 240aggtguagag utuauauutg agtgauatuy gtuaauauut gayggaguta guuygtgagt 300g 301321300DNAArtificial SequenceSynthetic polynucleotide 321uuaggutguu tgggttttgg tutuuauuat gutaguttgg tgtuygauut gtgttgagau 60uutuuutguu tutgguuygg gtgtuuuatu uaaguaatgg auaggttgga auaggygtty 120gtagggaayg ggutgaaygu uygyggutuu ygygatgtut ygygatauta uutuuutygu 180uuuygutuau ttaaggauyg gaagtaguaa aguuyguygt ygyguuuuuy guuuygygtu 240tuuutggtaa uuaguututu uuuttuuuty guuuataagg aguaagyggu auaaatyggg 300322300DNAArtificial SequenceSynthetic polynucleotide 322uuygatttgt guyguttgut uuttatgggy gagggaaggg gagaggutgg ttauuaggga 60gaygyggggy ggggggygyg ayggygggut ttgutauttu yggtuuttaa gtgagygggg 120gygagggagg tagtatygyg agauatygyg ggaguygygg gygttuaguu ygttuuutay 180gaayguutgt tuuaauutgt uuattguttg gatgggauau uyggguuaga gguagggagg 240gtutuaauau aggtyggaua uuaagutagu atggtggaga uuaaaauuua gguaguutgg 300323300DNAArtificial SequenceSynthetic polynucleotide 323uaatgguutu tttuttuagu utyggtgggy gtggutgggg gaauuuuagg gygggygggg 60gguagggggt ggtgutgagt uauuuaguut gguuaggtuu utguutguua guuuuutguu 120uuuauyguta uaguuyguuu yggatutayg agguuuaguu aguuauutut ggautuutga 180gauygaattg uaaautguuy ggguutgguu ttgaautuut gutgtttagg gauuaagtuu 240tgtggutuuu agggggguau agtgatutut uaagutgagu tgguutuagg guututguau 300324300DNAArtificial SequenceSynthetic polynucleotide 324tguagagguu utgagguuag utuaguttga gagatuautg tguuuuuutg ggaguuauag 60gauttggtuu utaaauagua ggagttuaag guuagguuyg gguagtttgu aattyggtut 120uaggagtuua gaggtggutg gutggguuty gtagatuygg ggygggutgt agyggtgggg 180guagggggut gguagguagg gauutgguua ggutgggtga utuaguauua uuuuutguuu 240uuyguuyguu utggggttuu uuuaguuayg uuuauygagg utgaagaaag agguuattgt 300325300DNAArtificial SequenceSynthetic polynucleotide 325auuutgtgua ggguutguat uuyggaaggu utuuauuagu uygaauutgg uuygtuyguu 60utagatgggg uaatyggygt ttutuuyggg auaguutuut uuutgguutu utgguuutyg 120tutguattga gagguttggu ututggtuyg uatgutguuu ttuuygtgut gtgguuttgu 180aguuygguut utuuuutgut gtuuuuuttg gututgguut gguuuutggg uuuutgagtu 240auuuutgagg tgautuagua gtuuttggaa ayguatguyg aggayguauu utguutgguu 300326300DNAArtificial SequenceSynthetic polynucleotide 326guuagguagg gtgygtuuty gguatgygtt tuuaaggaut gutgagtuau utuaggggtg 60autuaggggu uuagggguua gguuagaguu aagggggaua guaggggaga gguygggutg 120uaagguuaua guaygggaag gguaguatgy ggauuagagg uuaaguutut uaatguagay 180gaggguuagg agguuaggga ggaggutgtu uygggagaaa yguygattgu uuuatutagg 240gyggaygggu uaggttyggg utggtggagg uuttuyggga tguagguuut guauagggtt 300327300DNAArtificial SequenceSynthetic polynucleotide 327ggaauuattg ttutgutguu uauagutgyg tggagggatt uyggtuutyg ggttuagttg 60gtgauagtgt ygggtagguu tggguaggtg ggagaggtyg tgaaguuutt tguaggguau 120ttgguygutu atutgguaua ggggaagagg yguaguuygt gguuygguag tuuaggauut 180gutgttuuut tuutauuygg ggygggguut gtgggaagat atggaagtyg ggtgaatgag 240uygtguuuag tgattttaaa aaguagatta aaataauata gaaaatgtua gagutuattg 300328300DNAArtificial SequenceSynthetic polynucleotide 328uaatgagutu tgauattttu tatgttattt taatutgutt tttaaaatua utggguaygg 60utuattuauu ygauttuuat atuttuuuau agguuuyguu uygggtagga agggaauagu 120aggtuutgga utguyggguu aygggutgyg uututtuuuu tgtguuagat gagygguuaa 180gtguuutgua aaggguttua ygauututuu uauutguuua gguutauuyg auautgtuau 240uaautgaauu ygaggauygg aatuuutuua yguagutgtg gguaguagaa uaatggttuu 300329300DNAArtificial SequenceSynthetic polynucleotide 329guatuutuau utgygtuyga agyguagatg gaguuuaagg gaaagguuut gtagaggauu 60uygtgtgaut tgggguaaag ygtgguutuu uaggggtgyg tggguagygg gayguuuatg 120gtgtgauygg gtttgtguut uuatagggau ygtutguuut gtguagagag uuuutgtggg 180gygggaagtg gygaguaguy gguaaggagg uuuaguuaga uagaaguagg ggggtuaggg 240auatgggagg tgggggauua guuagtgagt uagaygtgag gauttuagtg uuaaggautg 300330300DNAArtificial SequenceSynthetic polynucleotide 330uagtuuttgg uautgaagtu utuaygtutg autuautggu tggtuuuuua uutuuuatgt 60uuutgauuuu uutguttutg tutggutggg uutuuttguy ggutgutygu uauttuuygu 120uuuauagggg utututguau aggguagayg gtuuutatgg agguauaaau uyggtuauau 180uatgggygtu uygutguuua yguauuuutg ggagguuayg utttguuuua agtuauaygg 240ggtuututau aggguutttu uuttgggutu uatutgygut tyggayguag gtgaggatgu 300331300DNAArtificial SequenceSynthetic polynucleotide 331aggttuuuua tuutagutuu uyggatutuu atagggagtg tuuagggauu utuaatutuu 60aggguuautt utguaggagu tygggttyga ggttuuaygt gguuagaaga gutuaggtut 120utgagggutg gtgtguuygg gtauuuatuy guatuautgu tutuutuutg tuyggutayg 180uuuagggutg agtgayggtg gtgguaagtg uttgtuutua ggguagygag gtuttutgtt 240utgauaguag uagggautuu ttuatgguua uuagtaauuu uagtgggygg aggygutuut 300332300DNAArtificial SequenceSynthetic polynucleotide 332aggagyguut uyguuuautg gggttautgg tgguuatgaa ggagtuuutg utgutgtuag 60aauagaagau utygutguuu tgaggauaag uauttguuau uauygtuaut uaguuutggg 120ygtaguygga uaggaggaga guagtgatgy ggatgggtau uyggguauau uaguuutuag 180agauutgagu tuttutgguu aygtggaauu tygaauuyga gutuutguag aagtgguuut 240ggagattgag ggtuuutgga uautuuutat ggagatuygg ggagutagga tggggaauut 300333300DNAArtificial SequenceSynthetic polynucleotide 333tuuttuuttu tttuuttutt tututututt ttutttuttt tuttttuttt tututtuttt 60uattttgaga ygtaututgg ututgtyguu uaggutggag yguaatggyg uuatutyggy 120guautguaau utuuauutuu ygggttuaag ygattutaut guutuaguut uuygagtagu 180tgggautaua ggygyguaut auuaaguuyg gutaattttt ttttgtattt ttagtagaga 240utgggtttua ygatgttggu ygggutggtu tggaagtutt gauutuaagy gtgyguuutu

300334300DNAArtificial SequenceSynthetic polynucleotide 334gagggyguay guttgaggtu aagauttuua gauuaguuyg guuaauatyg tgaaauuuag 60tututautaa aaatauaaaa aaaaattagu yggguttggt agtgygyguu tgtagtuuua 120gutautyggg aggutgaggu agtagaatyg uttgaauuyg ggaggtggag gttguagtgy 180guygagatgg yguuattgyg utuuaguutg ggygauagag uuagagtayg tutuaaaatg 240aaagaagaga aaagaaaaga aaagaaagaa aagagagaga aagaaggaaa gaaggaagga 300335300DNAArtificial SequenceSynthetic polynucleotide 335agguututgu tgauutgtag aauttgttga uuyggatttt gatgtuagtu tuattggguu 60tguygttgut uttuttggga uagaagatut utttgatuyg guuaattygg tagggutuag 120ggguatuuag gttgutguut ttgatgtagt yggagtattt uyggtagtgu tutgggtaua 180ggtuutuatu uaygggutuu ttuygtgggy gtttuayggg autggauagu ttgatgutgu 240agagaaguau uuauttgaua tuaatgaauu ttuuauuttg uagtggtuag tuagguatga 300336300DNAArtificial SequenceSynthetic polynucleotide 336tuatguutga utgauuautg uaaggtggaa ggttuattga tgtuaagtgg gtguttutut 60guaguatuaa gutgtuuagt uuygtgaaay guuuayggaa ggaguuygtg gatgaggauu 120tgtauuuaga guautauygg aaatautuyg autauatuaa agguaguaau utggatguuu 180utgaguuuta uygaattggu yggatuaaag agatuttutg tuuuaagaag aguaayggua 240gguuuaatga gautgauatu aaaatuyggg tuaauaagtt utauaggtua guagagguut 300337300DNAArtificial SequenceSynthetic polynucleotide 337ggggyggggt tygguygggg gyggygguag gauutgagua guuaggaggg utgggggaua 60gtuaggtuag guyggtggut auuygguygu tggagagggu yggatgguay gtgguauuaa 120guaaaaggag gutgaguuag aaaguaggga yggggutaga ygaguaaagu tggguaggag 180ggygagttgg gagggguyga guyggutgtg ygtggtuuut tgggaggagg gggtgtgguu 240aaguaaguua aauagttygg aggtuagtgu aaggauaaga uaguutgggu aaaygaguag 300338300DNAArtificial SequenceSynthetic polynucleotide 338utgutygttt guuuaggutg tuttgtuutt guautgauut uygaautgtt tgguttgutt 60gguuauauuu uutuutuuua agggauuayg uauaguyggu tygguuuutu uuaautyguu 120utuutguuua gutttgutyg tutaguuuyg tuuutguttt utggutuagu utuuttttgu 180ttggtguuay gtguuatuyg guuututuua gygguygggt aguuauyggu utgauutgau 240tgtuuuuuag uuutuutggu tgutuaggtu utguyguygu uuuygguyga auuuyguuuu 300339300DNAArtificial SequenceSynthetic polynucleotide 339ygagttggga gggguygagu yggutgtgyg tggtuuuttg ggaggagggg gtgtgguuaa 60guaaguuaaa uagttyggag gtuagtguaa ggauaagaua guutggguaa aygaguaggg 120gyggagygtg agaguagaut guauyggaty gutuagguua guuuaagutg aagaggaagg 180gguaagutuu agaaguaggg gygggguyga uuaauutygu agatutgutg ggygaagagu 240aguagutggg uuaguuygat gutgtguygg gguaggtagt utyggaggut guuuaggggu 300340300DNAArtificial SequenceSynthetic polynucleotide 340uuuutgggua guutuygaga utauutguuu ygguauagua tygggutggu uuagutgutg 60ututtyguuu aguagatutg ygaggttggt ygguuuyguu uutguttutg gaguttguuu 120uttuututtu aguttgggut gguutgagyg atuyggtgua gtutgututu aygutuyguu 180uutgutygtt tguuuaggut gtuttgtuut tguautgauu tuygaautgt ttgguttgut 240tgguuauauu uuutuutuuu aagggauuay guauaguygg utygguuuut uuuaautygu 300341300DNAArtificial SequenceSynthetic polynucleotide 341aauagguuua aguutgtggu aggtgggggt uauuuaguuu aggyguttuu uauuuuyggg 60uutggguuag aaguuuagga gutggutgyg gguyggttut uuuuuauuua ututggggat 120guutuagguu tgggtttuyg uuttaguuty guuagguuuu aatgaguutu tgtttgguut 180gtagtuaatt gauyggttgg auttggggua ggtgutygag gaguuuuaut gagggagggu 240aggtututtg tgygtautgt uuaguauata uaggaaattt aguatttutg uuuauuuagu 300342300DNAArtificial SequenceSynthetic polynucleotide 342gutgggtggg uagaaatgut aaatttuutg tatgtgutgg auagtaygua uaagagauut 60guuutuuutu agtggggutu utygaguauu tguuuuaagt uuaauyggtu aattgautau 120agguuaaaua gaggutuatt gggguutggy gaggutaagg yggaaauuua gguutgaggu 180atuuuuagag tgggtggggg agaauygguu yguaguuagu tuutgggutt utgguuuagg 240uuygggggtg ggaagyguut gggutgggtg auuuuuauut guuauaggut tggguutgtt 300343300DNAArtificial SequenceSynthetic polynucleotide 343uutgauuuau uuaaututuu uaggggaygt ggggguautg gaguuuuaua uyguaggygg 60tagutuaatg uauuygygty ggagttuutu uuuygygagy gtgguaaggu tuagggaagt 120uuyggguuuu tggggagggg guuttguygy guatuutgty guaggaauyg uyggguuutt 180uuttuygygg gaagyggutt gguygauuuu yguuuuyguu yggguututt gggggtttuy 240ggtguuyggu uauygtgggg utggggautg aaagtgatgg gautgaagat ggggutggaa 300344300DNAArtificial SequenceSynthetic polynucleotide 344ttuuaguuuu atuttuagtu uuatuauttt uagtuuuuag uuuuayggtg guyggguauy 60ggaaauuuuu aagagguuyg ggygggggyg ggggtygguu aaguyguttu uygyggaagg 120aaggguuygg yggttuutgy gauaggatgy gygguaaggu uuuutuuuua gggguuyggg 180auttuuutga guuttguuay gutygygggg gaggaautuy gaygygggtg uattgaguta 240uyguutgygg tgtggggutu uagtguuuuu aygtuuuutg ggagagttgg gtgggtuagg 300345300DNAArtificial SequenceSynthetic polynucleotide 345tatuuaaatg tgttttatat aaaatgaaty gttttuagtg uautgaggaa gttttutatt 60taaagaaatu utgutgtgaa ututtttgtg aagaatgutt tuutaatgga attagtuauu 120autgagtuat ttutguaaau ttuaggtttg yggttttguu taaguaagat utgguyggag 180aagtgagata aattatagat gtygutaata aattauagat tautuaaagg uaaaagagga 240aagaaaaaaa aaaattgaut ygtgtatatg aauygaattg agtuaggggt utuuauyggu 300346300DNAArtificial SequenceSynthetic polynucleotide 346guyggtggag auuuutgaut uaattyggtt uatatauayg agtuaatttt tttttttutt 60tuututtttg uutttgagta atutgtaatt tattagygau atutataatt tatutuautt 120utuygguuag atuttgutta gguaaaauyg uaaauutgaa gtttguagaa atgautuagt 180ggtgautaat tuuattagga aaguattutt uauaaaagag ttuauaguag gatttuttta 240aatagaaaau ttuutuagtg uautgaaaay gattuatttt atataaaaua uatttggata 300347300DNAArtificial SequenceSynthetic polynucleotide 347tgggagttuu agttyggggg uagauuagtg ttuagagtuy gggututgut autuagyguu 60ygagguagyg uutuuuuatt uaaygggggu ygtgguaatt uuutgauatg attuatgauu 120auataataua tuyggaaaut tututuuauy guutuuygtu tggguygtyg uuuuygguut 180gggagautuu aggtutuaga gtututguuu uuaygggyga tuagtgutgu uuagtggaaa 240aataatguua guygyguauu aaaattaggt gtaaaattaa uattttttgg aaguuauttt 300348300DNAArtificial SequenceSynthetic polynucleotide 348aagtgguttu uaaaaaatgt taattttaua uutaattttg gtgygyggut gguattattt 60ttuuautggg uaguautgat yguuygtggg gguagagaut utgagauutg gagtutuuua 120gguygggggy gaygguuuag aygggaggyg gtggagagaa gtttuyggat gtattatgtg 180gtuatgaatu atgtuaggga attguuaygg uuuuygttga atggggaggy gutguutygg 240gygutgagta guagaguuyg gaututgaau autggtutgu uuuygaautg gaautuuuat 300349300DNAArtificial SequenceSynthetic polynucleotide 349yggygtgutt uttgguaaau atutuuttga ggatguygut guaguauttg agutgutuyg 60agauuttgut gututtutut ggtgutgggt gutgutgaga gtyggguayg tuuttutttg 120gaggtttuau agguyggutg ututuuyguy gutgguuuag uttggtggtu ttgggutuyg 180gggguagyga gggtggutyg tgaatggggt uaatggtggt gggggtggtg gtgtutgutt 240tuututtuau tuuuttuttt gtutguuaag aauayggayg uuaauaggua uagtuagaag 300350300DNAArtificial SequenceSynthetic polynucleotide 350uttutgautg tguutgttgg ygtuygtgtt uttgguagau aaagaaggga gtgaagagga 60aaguagauau uauuauuuuu auuauuattg auuuuattua ygaguuauuu tygutguuuu 120yggaguuuaa gauuauuaag utggguuagy ggygggagag uaguygguut gtgaaauutu 180uaaagaagga ygtguuygau tutuaguagu auuuaguauu agagaagagu aguaaggtut 240yggaguagut uaagtgutgu agygguatuu tuaaggagat gtttguuaag aaguayguyg 300351300DNAArtificial SequenceSynthetic polynucleotide 351tggtutgutt uaagtuutau utgguuuutg guaagtuuua uttggtgaua tuttgtguut 60gggtuuttga gggutguuuu agatuygyga ttgtuutggg gauyggtagt tuutuuuygg 120atguuaguaa agutuuutuu aguutuuayg uutguauagt utuuagtatg uuttuaauag 180uuattagtua uuututgtga gtuagauuuu yggtuutguu agguuaauut guttgggguu 240tuaguagygg gggutggyga gguuagtttt utuuagyggt tutaaguygu tygagggtgg 300352300DNAArtificial SequenceSynthetic polynucleotide 352uauuutygag ygguttagaa uygutggaga aaautgguut yguuaguuuu ygutgutgag 60guuuuaagua ggttgguutg guaggauygg gggtutgaut uauagagggt gautaatggu 120tgttgaaggu atautggaga utgtguaggy gtggaggutg gagggagutt tgutgguatu 180yggggaggaa utauyggtuu uuaggauaat ygyggatutg ggguaguuut uaaggauuua 240gguauaagat gtuauuaagt gggauttguu agggguuagg taggauttga aguagauuag 300353300DNAArtificial SequenceSynthetic polynucleotide 353auutggtygg uuauygguag utyggggaag aagggygygt ggygyguuua utuuayggtg 60utgaagagua guygyguygu uagutyguau aygttgtyga tguuuaguau ygyguuyguy 120gyguyguuuu utgyguygaa gygtuygguy guyguagggt agggutuagy gyguaguagu 180tgygygatua gttyggauau yggutguuuy gggaagaggt utuyguygut yguuautguy 240guuagyguyg aguuyggggg gutguuygag gaggygguua ygguauuagg uagygagtgu 300354300DNAArtificial SequenceSynthetic polynucleotide 354guautygutg uutggtguyg tgguyguutu utyggguagu uuuuygggut yggygutggy 60gguagtggyg agyggyggag auututtuuy gggguaguyg gtgtuygaau tgatygygua 120gutgutgygy gutgaguuut auuutgyggy gguyggaygu ttyggyguag ggggyggygy 180ggygggygyg gtgutgggua tygauaaygt gtgygagutg gyggygyggu tgututtuag 240uauygtggag tgggygyguu aygyguuutt uttuuuygag utguyggtgg uygauuaggt 300355300DNAArtificial SequenceSynthetic polynucleotide 355tgguagagat auaaattuut gatgguagag gagggagaga gagtgtgggt gaygatgaua 60attgaautga gauuuaaagg aggtagggga gauatatggg ygtututggg aagatggtuu 120uygggaaagu auaguuttta gauagguuuy gagguaggag uutgtutgau tuauyggagg 180aguttggagg aggutgaggt gguutaagty gattaaguag ggtggggagg gaagaggyga 240tggtguygtg agauuaagua ggguuttgag gtutgggggg agaautttgg uttttautut 300356300DNAArtificial SequenceSynthetic polynucleotide 356gagtaaaagu uaaagttutu uuuuuagauu tuaagguuut guttggtutu aygguauuat 60yguututtuu utuuuuauuu tguttaatyg auttagguua uutuaguutu utuuaagutu 120utuyggtgag tuagauaggu tuutguutyg ggguutgtut aaaggutgtg utttuuyggg 180gauuatuttu uuagagaygu uuatatgtut uuuutauutu utttgggtut uagttuaatt 240gtuatygtua uuuauautut ututuuutuu tutguuatua ggaatttgta tututguuag 300357300DNAArtificial SequenceSynthetic polynucleotide 357agaggaggga gagagagtgt gggtgaygat gauaattgaa utgagauuua aaggaggtag 60gggagauata tgggygtutu tgggaagatg gtuuuyggga aaguauaguu tttagauagg 120uuuygaggua ggaguutgtu tgautuauyg gaggaguttg gaggaggutg aggtgguuta 180agtygattaa guagggtggg gagggaagag gygatggtgu ygtgagauua aguaggguut 240tgaggtutgg ggggagaaut ttggutttta ututgaggaa ggtgggaguu auagaggutt 300358300DNAArtificial SequenceSynthetic polynucleotide 358aguututgtg gutuuuauut tuutuagagt aaaaguuaaa gttutuuuuu uagauutuaa 60gguuutgutt ggtutuaygg uauuatyguu tuttuuutuu uuauuutgut taatygautt 120agguuauutu aguutuutuu aagutuutuy ggtgagtuag auaggutuut guutyggggu 180utgtutaaag gutgtguttt uuyggggauu atuttuuuag agayguuuat atgtutuuuu 240tauutuuttt gggtutuagt tuaattgtua tygtuauuua uautututut uuutuututg 300359300DNAArtificial SequenceSynthetic polynucleotide 359tgggygtutu tgggaagatg gtuuuyggga aaguauaguu tttagauagg uuuygaggua 60ggaguutgtu tgautuauyg gaggaguttg gaggaggutg aggtgguuta agtygattaa 120guagggtggg gagggaagag gygatggtgu ygtgagauua aguaggguut tgaggtutgg 180ggggagaaut ttggutttta ututgaggaa ggtgggaguu auagaggutt utagauagaa 240gaaggauaag uyggautuag gatauuaggg tgggggtatu tgtgggggat aaagggagaa 300360300DNAArtificial SequenceSynthetic polynucleotide 360ttutuuuttt atuuuuuaua gatauuuuua uuutggtatu utgagtuygg uttgtuuttu 60ttutgtutag aaguututgt ggutuuuauu ttuutuagag taaaaguuaa agttutuuuu 120uuagauutua agguuutgut tggtutuayg guauuatygu ututtuuutu uuuauuutgu 180ttaatygaut tagguuauut uaguutuutu uaagutuutu yggtgagtua gauaggutuu 240tguutygggg uutgtutaaa ggutgtgutt tuuyggggau uatuttuuua gagayguuua 300361300DNAArtificial SequenceSynthetic polynucleotide 361ggutttgtga aauuaauuag gaagaatgaa auauagagut ggtuygauau uuagutygag 60ggaggggggu yggaaguttu tggaagttgg utguuuutaa guagggguua ututaguuua 120uaagguuaag ttgguagagg uagaygaggg gaututgygg utuaagtuay ggguuaggag 180uuyguagutg uygggutgga aaggtuagag uyggututgy gtutggutgy guygguaaga 240aguuauaatt ayguagguaa aagaguuygg ggattaguuu uaguauutgg gauuutgaat 300362300DNAArtificial SequenceSynthetic polynucleotide 362attuagggtu uuaggtgutg gggutaatuu uygggututt ttguutgygt aattgtggut 60tuttguyggy guaguuagay guagaguygg ututgauutt tuuaguuygg uagutgyggg 120utuutgguuy gtgauttgag uyguagagtu uuutygtutg uututguuaa uttgguuttg 180tgggutagag tgguuuutgu ttagggguag uuaauttuua gaaguttuyg guuuuuutuu 240utygagutgg gtgtyggauu agututgtgt ttuattuttu utggttggtt tuauaaaguu 300363300DNAArtificial SequenceSynthetic polynucleotide 363aggutgaayg gaattgggag uagaguuutg yggtaggaua gagauttygu aaaguuygga 60guauauagua guauuuygtu ttutaaagga uaattttggg aaaaututtg uutaatattu 120tgguautaag gatuattutg tuauatuuuy gututggaut auaaguutgu aaguuuuatu 180ygggguaggg utuutuattu utgtguauyg tggaaguuut gtguutguuu aggguutggu 240auttgtaygt auttgaaaau utygtgtgga gtaaagagag gggtgatgtg uaaagguutt 300364300DNAArtificial SequenceSynthetic polynucleotide 364aagguutttg uauatuauuu utututttau tuuauaygag gttttuaagt aygtauaagt 60guuagguuut ggguagguau aggguttuua yggtguauag gaatgaggag uuutguuuyg 120gatggggutt guagguttgt agtuuagagy ggggatgtga uagaatgatu uttagtguua 180gaatattagg uaagagtttt uuuaaaattg tuutttagaa gayggggtgu tgutgtgtgu 240tuyggguttt gygaagtutu tgtuutauyg uagggututg utuuuaattu ygttuaguut 300365300DNAArtificial SequenceSynthetic polynucleotide 365aguuagguta aauuagygtg tuuuaatgag ggguuutggg utgagtggag gaaatgggtg 60yggtggaggt gggtttggut ggguauagyg gguaygtgtg ggtaagyggg tgggguyggt 120tgtgygggtg guutatutgg gguaaguagu ygagguygau tgtgtuyggy gtgtggttga 180guayggguag gtgtutggyg gtgauuutgu aygtutggtg tttauutggu uutgggtutg 240aygtggguyg yguutggutg utggygggau agtgtgttat utguutgygg ayguttuygg 300366300DNAArtificial SequenceSynthetic polynucleotide 366uyggaagygt uyguagguag ataauauaut gtuuyguuag uaguuaggyg ygguuuaygt 60uagauuuagg guuaggtaaa uauuagaygt guagggtuau yguuagauau utguuygtgu 120tuaauuauay guyggauaua gtygguutyg gutguttguu uuagataggu uauuyguaua 180auygguuuua uuyguttauu uauaygtguu ygutgtguuu aguuaaauuu auutuuauyg 240uauuuatttu utuuautuag uuuaggguuu utuattggga uaygutggtt taguutggut 300367300DNAArtificial SequenceSynthetic polynucleotide 367uuttggutua ggttggggag ggygtuatga gtuatgaggt gggygttgua tttgtuagtt 60gtguaguygy guauuauyga gtagtutggy gguagygygt uygygttyga ttgygtutgg 120uuyguaggag guuyggtuua guaguuuttu yguauuaggg tuauyggygy gygatauuut 180gggggyggga tyggggutyg tgututgutt uuygaaauuu ttutuuutuu agtutuagyg 240ttuttuutuu tuuututatu utttuauttt uauutauauu tuutuuuutu uutuuttuuu 300368300DNAArtificial SequenceSynthetic polynucleotide 368gggaaggagg gaggggagga ggtgtaggtg aaagtgaaag gatagaggga ggaggaagaa 60ygutgagaut ggagggagaa gggtttyggg aaguagagua ygaguuuyga tuuyguuuuu 120agggtatygy gyguyggtga uuutggtgyg gaagggutgu tggauygggu utuutgyggg 180uuagayguaa tygaaygygg aygygutguy guuagautau tyggtggtgy gyggutguau 240aautgauaaa tguaayguuu auutuatgau tuatgayguu utuuuuaauu tgaguuaagg 300369300DNAArtificial SequenceSynthetic polynucleotide 369uaggutggag tguaatggyg ygatutyggu tuautguaau ttutguutut ygggttuaag 60uaattuttut auuttaguut uutgagtagu tgggattaua ggtauutguy guuatguuyg 120gutaattttt taatttgttt ttagtagaga yggggtttua uuatgttggu uagguyggtu 180tauaautuut gatutuaggt gatutauuyg uutygguutu uuaaattaua ggtgttatua 240ttaggattut tgguagauag gagtgttgta ggggatggaa gtggatagta ggaggututg 300370300DNAArtificial SequenceSynthetic polynucleotide 370uagaguutuu tautatuuau ttuuatuuuu tauaauautu utgtutguua agaatuutaa 60tgataauauu tgtaatttgg gagguygagg ygggtagatu auutgagatu aggagttgta 120gauygguutg guuaauatgg tgaaauuuyg tututautaa aaauaaatta aaaaattagu 180yggguatggy gguaggtauu tgtaatuuua gutautuagg aggutaaggt agaagaattg 240uttgaauuyg agagguagaa gttguagtga guygagatyg yguuattgua utuuaguutg 300371300DNAArtificial SequenceSynthetic polynucleotide 371tgaatgauut ggguaguatt tutuuauutg yguttguatt tgutagauag tutgtgautu 60tutgtgggag aaaauauaag aaauygguuu ututgutggt tuuuuauutg guutggutut 120uutgttutuu auuutguaua utuatguuty ggaauutgut tutuututga guutuuutua 180uagtgguuyg guuuaygtgg uutttaatut guuuauatua gaguutuuau utuygguuta 240tgguuuatua gagguagutg gaguygggua tuutuuuuay gtggguuttt gaggatggga 300372300DNAArtificial SequenceSynthetic polynucleotide 372tuuuatuutu aaagguuuay gtggggagga tguuyggutu uagutguutu tgatggguua 60tagguyggag gtggaggutu tgatgtgggu agattaaagg uuaygtgggu yggguuautg 120tgagggaggu tuagaggaga aguaggttuy gagguatgag tgtguagggt ggagaauagg 180agaguuaggu uaggtgggga auuaguagag ggguyggttt uttgtgtttt utuuuauaga 240gagtuauaga utgtutagua aatguaagyg uaggtggaga aatgutguuu aggtuattua 300373300DNAArtificial SequenceSynthetic polynucleotide 373gggygggguu tgtgyggtut gyggygygga guygagtggg utgyggggat gygggggauu 60agutgygtgg gyggyggygu ygagaguuuy ggaggygygg ggutgagyga ggguuygygg 120gggygutggu tgyguttggu tuyggtatgy guutauttuu tutgygtuty gutagutguy 180gtgutgutyg uygtgtauta yggtutuatu tgggtauuua ygyggtutuu ygygguauuy 240guygguuuau aguuuagygy guygtuuuut uygtgtgutg uuyguuyggg ygtguyguut 300374300DNAArtificial SequenceSynthetic polynucleotide 374aggygguayg uuygggyggg uaguauaygg aggggayggy gygutgggut gtggguyggy 60gggtguygyg ggagauygyg tgggtauuua gatgagauyg tagtauaygg ygaguaguay 120gguagutagy gagayguaga ggaagtaggy guatauygga guuaagygua guuagyguuu 180uygyggguuu tygutuaguu uygyguutuy ggggututyg gyguyguygu uuayguagut 240ggtuuuuygu atuuuyguag uuuautyggu tuygyguygu agauyguaua gguuuyguuu 300375300DNAArtificial SequenceSynthetic polynucleotide 375aagtgtattt tuaaggtatg agggguuuag aggauautgt uuuaaaagua gtggttgtga 60gagtgguttt ggagtuaggu tgauagtutg gaaauttuua ggtuygutut gaagtguygg 120utguatgauu aguuutuuag uutgtgtuyg uttygguutt utttgtguaa gtgagaguat 180tgutgatuuu uuyggggtgg ygagggggyg uaygtuagtg auutyguatg gtguutguua 240gguaygtggt

uygtgtttua tgattutttg agagutttgg aguagutuua agaagautut 300376300DNAArtificial SequenceSynthetic polynucleotide 376gagtuttutt ggagutgutu uaaagututu aaagaatuat gaaauaygga uuaygtguut 60gguagguauu atgygaggtu autgaygtgy guuuuutygu uauuuygggg ggatuaguaa 120tgututuaut tguauaaaga agguygaagy ggauauaggu tggagggutg gtuatguagu 180ygguauttua gagyggauut ggaagtttuu agautgtuag uutgautuua aaguuautut 240uauaauuaut guttttggga uagtgtuutu tggguuuutu atauuttgaa aatauauttt 300377300DNAArtificial SequenceSynthetic polynucleotide 377taattttaaa uaaaaututu uatgaguaau taaatattta aaatgtgttt ttuuataaaa 60gtgaatuagu tuagttutgu aggutgaaaa tauaauaagg aggatuyggg ttguagaaag 120uagaggguua uutagauygt gtutgagaga yggggagaaa guagutgtut gutgtguauu 180agagguutut agggauuuyg guaguaauuu ygtggygggu uauauttggg agutgatttg 240ttttuagaau uauuagutaa guuauatgag uuaggaguut ggttatuuat tuaaaguuua 300378300DNAArtificial SequenceSynthetic polynucleotide 378tgggutttga atggataauu aggutuutgg utuatgtggu ttagutggtg gttutgaaaa 60uaaatuagut uuuaagtgtg guuyguuayg gggttgutgu yggggtuuut agagguutut 120ggtguauagu agauagutgu tttutuuuyg tututuagau ayggtutagg tgguuututg 180utttutguaa uuyggatuut uuttgttgta ttttuaguut guagaautga gutgattuau 240ttttatggaa aaauauattt taaatattta gttgutuatg gagagttttg tttaaaatta 300379300DNAArtificial SequenceSynthetic polynucleotide 379guutuuagau uygaaatuuu uuautgaagu uattuuuagg aggagggguu tuautggggu 60utuaagguag uatuaguatt tuyggtgaua gguauaguaa tttatuagut uautggutut 120utautgagaa uaagguaagu ygggguutgu ygagggtatg auagguaggg agtgatgggu 180uygguuuagg guaggaggga gauagaaatg gguaggaaga ggaggutgtu uuuaguagua 240uttutgagag gaggaguauu tttyggggau aututggayg guauuuuuaa guauaguuuu 300380300DNAArtificial SequenceSynthetic polynucleotide 380ggggutgtgu ttgggggtgu ygtuuagagt gtuuuygaaa ggtgutuutu ututuagaag 60tgutgutggg gauaguutuu tuttuutguu uatttutgtu tuuutuutgu uutggguygg 120guuuatuaut uuutguutgt uatauuutyg guagguuuyg guttguuttg ttutuagtag 180agaguuagtg agutgataaa ttgutgtguu tgtuauygga aatgutgatg utguuttgag 240guuuuagtga gguuuutuut uutgggaatg guttuagtgg gggatttygg gtutggaggu 300381300DNAArtificial SequenceSynthetic polynucleotide 381tgagaguagu uagauaygta gtgatuaggg aaagtygaaa gtguagatgg gttyguaaay 60gtggaututu tagttttggg tutguagatg ggguygguua uuaygtgutu tutgagttut 120utttuuaagt auagatuuut uyggagaygg aauattgttu yguutttaat tuttuuuagg 180agutgyggag gaaggygtga gaauyggagu uyggggtgau ttgyggggga ggggatygut 240tuuuygtygu uuauauutgu utaauuuayg uuuayggygg uyguaaaggy gauauygygt 300382300DNAArtificial SequenceSynthetic polynucleotide 382aygyggtgty guutttgygg uyguygtggg ygtgggttag guaggtgtgg gygaygggga 60agygatuuuu tuuuuyguaa gtuauuuygg gutuyggttu tuayguuttu utuyguagut 120uutgggaaga attaaaggyg gaauaatgtt uygtutuygg agggatutgt auttggaaag 180agaautuaga gaguaygtgg tgguygguuu uatutguaga uuuaaaauta gagagtuuay 240gtttgygaau uuatutguau tttygauttt uuutgatuau taygtgtutg gutgututua 300383300DNAArtificial SequenceSynthetic polynucleotide 383auaagyggtt ggatttygag aggauatuaa gaguaygtua agaguaygtu aagaguauay 60ggauagguau tgguayguyg guaggtuatt gauygguaga auagagtttg guuagggutg 120tuagagaaga gtyggguygu uaaguaguuy gauttuuagy ggaaaauuat utguuttutg 180gutuutuuat utgutgagag utauttuuau tuaataaaau uttguautua ttutuuaaau 240uuauatgaga tuuaattutt uyggtauauu aagguaggaa uuuygagata uagaaaguuu 300384300DNAArtificial SequenceSynthetic polynucleotide 384gggutttutg tatutygggg ttuutguutt ggtgtauygg aagaattgga tutuatgtgg 60gtttggagaa tgagtguaag gttttattga gtggaagtag ututuaguag atggaggagu 120uagaagguag atggttttuy gutggaagty gggutguttg gygguuygau tuttututga 180uaguuutggu uaaaututgt tutguyggtu aatgauutgu yggygtguua gtguutgtuy 240gtgtgututt gaygtgutut tgaygtgutu ttgatgtuut utygaaatuu aauyguttgt 300385300DNAArtificial SequenceSynthetic polynucleotide 385auttgaagtu aggagttygt gaauaguutg guuaauatgg tgaaauuutg tututautaa 60aaaaagaaaa attaguyggg tgtggtgggy guutgtaauu uuaguauttt gggaggutga 120ggtgggtgga tuauttgaag tuaggagtty gtgaauaguu tgatuaauat ggtgaaauuu 180tgtututaut aaaaauauaa aaattaguyg ggtgtggtgg tgggtguutg taatuuuagu 240tautuaggag autgagguag gaggatuaut tgaauygggg agguagaggt tguagagagt 300386300DNAArtificial SequenceSynthetic polynucleotide 386utututguaa uututguutu uuyggttuaa gtgatuutuu tguutuagtu tuutgagtag 60utgggattau agguauuuau uauuauauuy ggutaatttt tgtgttttta gtagagauag 120ggtttuauua tgttgatuag gutgttuayg aautuutgau ttuaagtgat uuauuuauut 180uaguutuuua aagtgutggg gttauaggyg uuuauuauau uyggutaatt tttutttttt 240tagtagagau agggtttuau uatgttgguu aggutgttua ygaautuutg auttuaagtg 300387300DNAArtificial SequenceSynthetic polynucleotide 387aaatuttttt uutguutgua ttttuttaua taaaguaatu tautautguu atyggttuat 60tuautuauyg gaauutgtut tguuaggauu tgauutuagu agautgagtu atauuaguat 120uatuuttgtt gggguuuagg tutguatuuy guttuygguu uuaguuuuau tgttagutuu 180atuaggtuut utgggguaua uuaaggaggu ygttttutut uuutttttut gaattagatu 240uuuagaaaua agauatuagg uttuutgggg aaatutaatt ttgutuatga atttgauuat 300388300DNAArtificial SequenceSynthetic polynucleotide 388atggtuaaat tuatgaguaa aattagattt uuuuaggaag uutgatgtut tgtttutggg 60gatutaattu agaaaaaggg agagaaaayg guutuuttgg tgtguuuuag aggauutgat 120ggagutaaua gtggggutgg gguyggaagy gggatguaga uutggguuuu aauaaggatg 180atgutggtat gautuagtut gutgaggtua ggtuutggua agauaggttu yggtgagtga 240atgaauygat gguagtagta gattguttta tgtaagaaaa tguagguagg aaaaagattt 300389300DNAArtificial SequenceSynthetic polynucleotide 389uaaggtuuag gtuuuaguut uuuuauyguy guuygyguuu tuutagguut yggagyggyg 60uutttutgyg guutygaagg tggggtggga aagtttgggg agtuuyggut utuauaguut 120gtygtgagaa utguuuuygg ggaattygtu yguygtaygg aaaaautggu yggaguagag 180tygtuygygg ttuygyggty gygggtggaa ggtgaaggty gagggaggtu aggutguttu 240tgygtgtuut gayggutggy gtgttututt gagatgggut ygggutautt gguuaguttu 300390300DNAArtificial SequenceSynthetic polynucleotide 390gaagutgguu aagtaguuyg aguuuatutu aagagaauay guuaguygtu aggauaygua 60gaaguaguut gauutuuuty gauuttuauu ttuuauuygy gauygyggaa uygyggayga 120ututgutuyg guuagttttt uygtayggyg gaygaattuu uyggggguag ttutuaygau 180aggutgtgag aguygggaut uuuuaaautt tuuuauuuua uuttygaggu yguagaaagg 240yguygutuyg agguutagga gggygygggy ggyggtgggg aggutgggau utggauuttg 300391300DNAArtificial SequenceSynthetic polynucleotide 391uygagggagu uagguuauag utgauaggaa gguagaaggt gguaggaggg gaggttgygu 60tguauututg ggttguuuag guuaauutgu uagguaggag ggggaaguuy gtguuuautt 120tauuatgauy gggaagatga tgguaguuau ygtggatttg aggatuuaga guauyguuag 180guagaggatu tguauuaggg tgaagaggtg gatuyggygu agygguaygt guyguaggaa 240gguatggtuy ggutggtgut tggutgguat uaggaagagu ttguagygtt uuuagaauta 300392300DNAArtificial SequenceSynthetic polynucleotide 392tagttutggg aaygutguaa gututtuutg atguuaguua aguauuaguy ggauuatguu 60ttuutgyggu aygtguygut gyguyggatu uauututtua uuutggtgua gatuututgu 120utggyggtgu tutggatuut uaaatuuayg gtggutguua tuatuttuuy ggtuatggta 180aagtggguay ggguttuuuu utuutguutg guaggttggu utggguaauu uagaggtgua 240gyguaauutu uuutuutguu auuttutguu ttuutgtuag utgtgguutg gutuuutygg 300393300DNAArtificial SequenceSynthetic polynucleotide 393aaattauuyg ggygtggtgg tgggtguutg taatuuuagu tautuaggag guygagguag 60gagaauygut tgaauuyggg agguagagua taggttgttg gagggttgaa ggtguauuua 120guagagautg guatauagga ggtuutguaa ygguuuuagg aaauututgg gtuuagtaag 180aguttuagua ggaggtagaa uuatauyggg uaggagtguu tggaaaggut tuaagguaau 240tuuutuuaaa gtuutgguuu aauuutauau tgtuaggutg ttaaagguua tttaaaagut 300394300DNAArtificial SequenceSynthetic polynucleotide 394aguttttaaa tgguutttaa uaguutgaua gtgtagggtt ggguuaggau tttggaggga 60gttguuttga aguutttuua gguautuutg uuyggtatgg ttutauutuu tgutgaagut 120uttautggau uuagaggttt uutgggguyg ttguaggauu tuutgtatgu uagtututgu 180tgggtguauu ttuaauuutu uaauaauuta tgututguut uuygggttua agyggttutu 240utguutyggu utuutgagta gutgggatta uagguauuua uuauuayguu ygggtaattt 300395300DNAArtificial SequenceSynthetic polynucleotide 395aggaaaaaau aguaguuuaa gaatyggguu tuuutgttau aguaggagty guatutattt 60atatatgtta tgtuttattg utuaguaauu agututyggu yggggygtgg guygggaaga 120ggggtutuut ggtguagygg gttggygtga utuatuauyg uygyguautu tgguututgg 180guutaggtta auagautuuy gggtttuagg utggguuuag gygguuaggu uutuuutgut 240gaggaatutg ggttggggua gtguuagutu uutguttutu auutgguuau agaaggggta 300396300DNAArtificial SequenceSynthetic polynucleotide 396tauuuuttut gtgguuaggt gagaaguagg gagutgguau tguuuuaauu uagattuutu 60aguagggagg guutgguygu utggguuuag uutgaaauuy gggagtutgt taauutaggu 120uuagagguua gagtgygygg yggtgatgag tuayguuaau uygutguauu aggagauuuu 180tuttuuyggu uuayguuuyg guygagagut ggttgutgag uaataagaua taauatatat 240aaatagatgy gautuutgut gtaauaggga gguuygattu ttgggutgut gttttttuut 300397300DNAArtificial SequenceSynthetic polynucleotide 397auuuaggaat tutttttttt ttttttttga gayggygtut utgtyguuua ggutggagtg 60uagtggygua gtutyguuta autguaagut uyguuuuygg gttuatguua ttutuutguu 120tuaguututt gagtagutgg aautauaggy guutguuauu auauuygguu aattttttgt 180atttttagta gagayggggt ttuauygtgt taguuaggat ggtutygatu tuutgauuty 240gtgatuuauu uauutuaguu tutuaaagtg utgggattau agguttgaau uautgyguuu 300398300DNAArtificial SequenceSynthetic polynucleotide 398gggyguagtg gttuaaguut gtaatuuuag uautttgaga ggutgaggtg ggtggatuay 60gaggtuagga gatygagauu atuutgguta auayggtgaa auuuygtutu tautaaaaat 120auaaaaaatt gguygggtgt ggtgguaggy guutgtagtt uuagutautu aagaggutga 180gguaggagaa tgguatgaau uygggggygg aguttguagt taggygagau tgyguuautg 240uautuuaguu tgggygauag agayguygtu tuaaaaaaaa aaaaaaaaga attuutgggt 300399300DNAArtificial SequenceSynthetic polynucleotide 399aaatauagua ggagagaatt uututgagau utaagatauy gtguuuttuu uuuttgguut 60utuagutgut guygagtuut ggagaaaaty ggguatutga auagagguyg tgtttgtuuu 120tgutuygguu ttgtgttutu attuutguua yguuatuatg gataatgaaa gttgautggu 180tguyggggtt tuutttutut utguuuutgt uatttuuatt tguuaggtut uatguutttt 240ttguauagag ttgttgtgut tgggututaa tttguuaggu agtgataaat tuuaagaaaa 300400300DNAArtificial SequenceSynthetic polynucleotide 400ttttuttgga atttatuaut guutgguaaa ttagaguuua aguauaauaa ututgtguaa 60aaaagguatg agauutggua aatggaaatg auagggguag agagaaagga aauuuyggua 120guuagtuaau tttuattatu uatgatggyg tgguaggaat gagaauauaa gguyggagua 180gggauaaaua ygguututgt tuagatguuy gattttutuu aggautyggu aguagutgag 240agguuaaggg ggaaggguay ggtatuttag gtutuagagg aattututuu tgutgtattt 300401300DNAArtificial SequenceSynthetic polynucleotide 401guuutgagau autaaatggy gggggggtgg ggggaggaaa gggaaggygg uagagutuuu 60ygaguyggga uagtuautta ututauaggu agtgggguuy gauauagaua gyguyguuuu 120yguuaguuag uutyguaygu uutyggaagy guaggutuuy ggygutgygu tggagggttu 180uuygguauuu uaguutuuyg tuuuuaguuy gutguauutu yggguuuuuu ttauuuttga 240gagguauygg gagttgtygy ggggggguut ygggaaattu uuyggauuuu tgtguuagga 300402300DNAArtificial SequenceSynthetic polynucleotide 402tuutgguaua ggggtuyggg gaatttuuyg agguuuuuuy gygauaautu uyggtguutu 60tuaagggtaa gggggguuyg gaggtguagy gggutgggga ygggaggutg gggtguyggg 120gaauuutuua gyguagyguy gggaguutgy guttuygagg gygtgygagg utggutggyg 180ggggyggygu tgtutgtgty ggguuuuaut guutgtagag taagtgautg tuuyggutyg 240gggagututg uyguuttuuu tttuutuuuu uuauuuuuuy guuatttagt gtutuagggu 300403300DNAArtificial SequenceSynthetic polynucleotide 403auuauaguau tguaggagga tgaguuuutg uaggaaggaa tgutggutut utggggtaga 60taaagaaggt tutggggaag ggaagggagg aauaggaaua tgggutuuut guuaggutgt 120uuuaggtuyg ggatguuaty gguaagtggg yggggauagg uutgggtaga tgauatggta 180gtgagtaagt ggggagguag guuaguagag gaguuaggut uauutuuygu uyguuuauut 240ygguuauaga uygggagggg tyggaguaut gygttggggt tgatgaguag aygautguua 300404300DNAArtificial SequenceSynthetic polynucleotide 404tgguagtygt utgutuatua auuuuaaygu agtgutuyga uuuutuuygg tutgtgguyg 60aggtgggygg gygggaggtg aguutggutu ututgutggu utguutuuuu auttautuau 120tauuatgtua tutauuuagg uutgtuuuyg uuuauttguy gatgguatuu yggauutggg 180auaguutggu agggaguuua tgttuutgtt uutuuuttuu uttuuuuaga auuttuttta 240tutauuuuag agaguuagua ttuuttuutg uaggggutua tuutuutgua gtgutgtggt 300405300DNAArtificial SequenceSynthetic polynucleotide 405agggaaggga ggaauaggaa uatgggutuu utguuaggut gtuuuaggtu ygggatguua 60tygguaagtg ggyggggaua gguutgggta gatgauatgg tagtgagtaa gtggggaggu 120agguuaguag aggaguuagg utuauutuuy guuyguuuau utygguuaua gauygggagg 180ggtyggagua utgygttggg gttgatgagu agaygautgu uagguaguua ttuauaggaa 240atgguauaga yguauattgt tuuagutauu uuuuatuutu uutuaggggu aaagtgaatg 300406300DNAArtificial SequenceSynthetic polynucleotide 406attuautttg uuuutgaggg aggatggggg gtagutggaa uaatgtgygt utgtguuatt 60tuutgtgaat ggutguutgg uagtygtutg utuatuaauu uuaayguagt gutuygauuu 120utuuyggtut gtgguygagg tgggygggyg ggaggtgagu utggutuutu tgutgguutg 180uutuuuuaut tautuautau uatgtuatut auuuagguut gtuuuyguuu auttguygat 240gguatuuygg auutgggaua guutgguagg gaguuuatgt tuutgttuut uuuttuuutt 300407300DNAArtificial SequenceSynthetic polynucleotide 407ggttutaaau auauaaauut ttgatguatu tggaatttau uttaatttuu taguaatttt 60tatuaatggu tuaatatttg ggggattttu atggtaattg uautgaatgt attaautggt 120uagggaggat tauatuaaga uuauygguty gagaaauagu agtutgttuu tuuauuuuua 180ygtutguatu uagguuuttu uauagagatu tuatttutuu tguagatgau tuattuagtg 240tutaggaatu yggtgututg tgguuautau ygagagtggg atattttuuu uuattttatt 300408300DNAArtificial SequenceSynthetic polynucleotide 408aataaaatgg gggaaaatat uuuaututyg gtagtgguua uagaguauyg gattuutaga 60uautgaatga gtuatutgua ggagaaatga gatututgtg gaaggguutg gatguagayg 120tgggggtgga ggaauagaut gutgtttuty gaguyggtgg tuttgatgta atuutuuutg 180auuagttaat auattuagtg uaattauuat gaaaatuuuu uaaatattga guuattgata 240aaaattguta ggaaattaag gtaaattuua gatguatuaa aggtttgtgt gtttagaauu 300409300DNAArtificial SequenceSynthetic polynucleotide 409tttggggggu agggagggtt uagtuuuutu agguutggut gtgtuuuutg uuuuuuauuu 60auaatuaggu uuagggttgg ggggtguaua uuaaggaggg guaggaagtg tuuaagaagu 120agaauyggut utgtgtuuuu agtggyggyg ggtgtutggg guaggaggag gutatutgat 180uuuttuuuua utguuuyggu uatgauutuu tuuutuuutu uutygutuuu tuuutuuutu 240uutuuutuuu tuuutuuutu uutuutuutt uatggutggg gtaguuagua uuutgggutg 300410300DNAArtificial SequenceSynthetic polynucleotide 410aguuuagggt gutggutauu uuaguuatga aggaggaggg agggagggag ggagggaggg 60agggagggag ggagygaggg agggagggag gaggtuatgg uygggguagt ggggaaggga 120tuagataguu tuutuutguu uuagauauuy guyguuautg gggauauaga guyggttutg 180uttuttggau auttuutguu uutuuttggt gtguauuuuu uaauuutggg uutgattgtg 240ggtggggggu aggggauaua guuagguutg aggggautga auuutuuutg uuuuuuaaag 300411300DNAArtificial SequenceSynthetic polynucleotide 411uuyguaaguu tyguuuutuu agguutyguu utuuutuutt guagagagtg guuaagutyg 60tgttuuagag gutgaatgag gattttgtgy ggaaguuyga utatgutttg agututgtgg 120gtaagauuyg gagauautgg aagauagaga yguagauagg aaagagguua agauautgau 180auagauagau uuatguauut gauygguyga agauagaguu tyggauaguu uuuauuyguu 240uuuaguuuuy gyguuuuygy guuuygautu uygguaaggu utgggaguut utgagggtta 300412300DNAArtificial SequenceSynthetic polynucleotide 412taauuutuag aggutuuuag guuttguygg gagtyggggy gygggggygy gggggutggg 60ggygggtggg ggutgtuyga ggututgtut tygguyggtu aggtguatgg gtutgtutgt 120gtuagtgtut tgguututtt uutgtutgyg tututgtutt uuagtgtutu ygggtuttau 180uuauagagut uaaaguatag tyggguttuy guauaaaatu utuattuagu ututggaaua 240ygaguttggu uautututgu aaggagggag ggygagguut ggaggggyga gguttgyggg 300413300DNAArtificial SequenceSynthetic polynucleotide 413uagatuaggg tuutuagaut tgtuyggagg gaggguuutg uatauutguu aayguuutgt 60ttgutgggaa aggggutgat gttguaatga uaggttaaau aguaauagga uattgautgg 120uatutguaag utgagutuag utuagagagg ygaggaguau aggggaggga ggaaaatuuy 180ggtgtggatu tuauuuauay gguuuautgg gtgutuutgg uagayggaat tatgggtgut 240tttaututut uattttaaaa atgtgutttt tatgtgtatt gtaaaagtaa uagattuuua 300414300DNAArtificial SequenceSynthetic polynucleotide 414tgggaatutg ttauttttau aatauauata aaaaguauat ttttaaaatg agagagtaaa 60aguauuuata attuygtutg uuaggaguau uuagtggguy gtgtgggtga gatuuauauy 120gggattttuu tuuutuuuut gtgutuutyg uutututgag utgagutuag uttguagatg 180uuagtuaatg tuutgttgut gtttaauutg tuattguaau atuaguuuut ttuuuaguaa 240auagggygtt gguaggtatg uaggguuutu uutuyggaua agtutgagga uuutgatutg 300415300DNAArtificial SequenceSynthetic polynucleotide 415uauttggutu tygtggutgg gauagattgu ttuuttuutu tutuutgggt guuaggtagg 60uuuagaaauu auutgatgtu aguaagguut gguuauuuau tggtggggag gaagtgggyg 120ggtguuuagg gauagatgag uyggguagay gtguuutgag guaguauagt uagggutgay 180gtggguatta tguauutygg ggutttuaga gutggutuyg gtuuygtttg uuuauatuaa 240guaggtuaga gtggagaggg uuaggggygu tggggtuaag guatguautg auuaggygtu 300416300DNAArtificial SequenceSynthetic polynucleotide 416gayguutggt uagtguatgu uttgauuuua gyguuuutgg uuututuuau tutgauutgu 60ttgatgtggg uaaaygggau yggaguuagu tutgaaaguu uygaggtgua taatguuuay 120gtuaguuutg autgtgutgu utuaggguay gtutguuygg utuatutgtu uutggguauu 180yguuuauttu utuuuuauua gtgggtgguu agguuttgut gauatuaggt ggtttutggg 240uutauutggu auuuaggaga gaggaaggaa guaatutgtu uuaguuayga gaguuaagtg 300417300DNAArtificial SequenceSynthetic polynucleotide 417atuuauautt gaauatauag auatuutttt uuagggtgtg ttgtgutyga tauutttaat 60tuutgtutgu attuuagggu utguuuaguu tuttuutggu tuuuuaguuu aguutggtuu 120ttuygguutu uutgtuatuu uuauututyg tgtgtguaua aguagggauu aggtagggag 180auygguagat

gutgututut gtuuutgggg tttuttttut tagtgttgut uuuauauuua 240ygygatgutt taattaautg uuauautuag gutttutuag tggggagagt uagaaataga 300418300DNAArtificial SequenceSynthetic polynucleotide 418utatttutga ututuuuuau tgagaaaguu tgagtgtggu agttaattaa aguatygygt 60gggtgtggga guaauautaa gaaaagaaau uuuagggaua gagaguagua tutguyggtu 120tuuutauutg gtuuutgutt gtguauauay gagaggtggg gatgauaggg agguyggaag 180gauuaggutg ggutggggag uuaggaagag gutggguagg uuutggaatg uagauaggaa 240ttaaaggtat ygaguauaau auauuutgga aaaggatgtu tgtatgttua agtgtggatg 300419300DNAArtificial SequenceSynthetic polynucleotide 419tuuuaguuau tuyguagtua utuutgauuu agaaaagaau aauuauagut ggguuuagua 60uuuyggguua utuuutguag utguuuauau atutgguagu tgggtuuaut tatguaatgt 120ggatygggut tuttauatut gaaatutgyg tututatuuu tuututgaga uuagtgtutu 180utguuagutt uuatgguuuy gggatgauut uaututuuua gggtutuuut gygtuutggg 240agututgguy gaggaguagu aggggutgat gguagagygg ggguaggtua gagutuagua 300420300DNAArtificial SequenceSynthetic polynucleotide 420gutgagutut gauutguuuu ygututguua tuaguuuutg utgutuutyg guuagagutu 60uuaggaygua gggagauuut gggagagtga ggtuatuuyg ggguuatgga agutgguagg 120agauautggt utuagaggag ggatagagay guagatttua gatgtaagaa guuygatuua 180uattguataa gtggauuuag utguuagatg tgtggguagu tguagggagt gguuyggggt 240gutggguuua gutgtggttg ttuttttutg ggtuaggagt gautgyggag tggutgggau 300421300DNAArtificial SequenceSynthetic polynucleotide 421uuaaaygygg uauaygggga ygguuuutuu yggggtuagg utuautggut uuttuuuttu 60agyguuauua gguaggaggg uuaayggtua uauaggaggu auuutuauut guutttguau 120uaguaaataa agtguatuuu attttygtgt gagygtyggu uyggtgagtu aguuuttuyg 180gguuutttuu tgttutuagg guagggggyg tgygutgagu uagaggtaga tutguagaaa 240ggguuuygau tggguutygg guaggguygg yguuuauuau aututggggg tuagutatgu 300422300DNAArtificial SequenceSynthetic polynucleotide 422guatagutga uuuuuagagt gtggtgggyg uygguuutgu uygagguuua gtygggguuu 60tttutguaga tutauututg gutuagygua yguuuuutgu uutgagaaua ggaaaggguu 120yggaagggut gautuauygg guygaygutu auaygaaaat gggatguaut ttatttgutg 180gtguaaaggu aggtgagggt guutuutgtg tgauygttgg uuutuutguu tggtggygut 240gaagggaagg aguuagtgag uutgauuuyg ggagggguyg tuuuygtgtg uygygtttgg 300423300DNAArtificial SequenceSynthetic polynucleotide 423guaggaaggg uuuagaygau auuuuuauag auatatguua guuuutuygg gtgauuaaaa 60tuatutuagt aaagguagat gagguuaagy gaaaaggggt gggtggaaga auyggututg 120agtutuaguu uauagauaut yggauautyg tygguuyggt agguaggggt tuutggtggu 180utuaggutgt uagguuyggu uuuutuuygu agutgtutuu agutuuuauu tuuuuyguuu 240auuuuuuagg autuutattt uautgaggag attaagauua uutggygaga auuuutuuua 300424300DNAArtificial SequenceSynthetic polynucleotide 424gggaggggtt utyguuaggt ggtuttaatu tuutuagtga aataggagtu utggggggtg 60ggygggggag gtgggagutg gagauagutg ygggaggggg uyggguutga uaguutgagg 120uuauuaggaa uuuutguuta uyggguygay gagtgtuyga gtgtutgtgg gutgagautu 180agaguyggtt uttuuauuua uuuuttttyg uttgguutua tutguuttta utgagatgat 240tttggtuauu yggaggggut gguatatgtu tgtgggggtg tygtutgggu uuttuutgut 300425300DNAArtificial SequenceSynthetic polynucleotide 425aggtgagatu tggaggttgy gggguagtta guaagtggga gagagutgua tgyggggaag 60gtgggaggyg ttguaggaaa ggtgagggag auauagutga gutgtggtgu tgguuagutg 120ggguuttgyg uuttatuygg guautgtgay gguuautaau aggttttaag tauyggaatg 180auatgatygg atttgtaatt taautagatu uttutgautg utgttggggg aauagautgt 240uaauutuaua auaguautgt uagutgagta ttagauaaat gatgaauutg gguuuaggga 300426300DNAArtificial SequenceSynthetic polynucleotide 426uuutggguuu aggttuatua tttgtutaat autuagutga uagtgutgtt gtgaggttga 60uagtutgttu uuuuaauagu agtuagaagg atutagttaa attauaaatu ygatuatgtu 120attuyggtau ttaaaauutg ttagtgguyg tuauagtguu yggataaggy guaagguuuu 180agutgguuag uauuauagut uagutgtgtu tuuutuauut ttuutguaay guutuuuauu 240ttuuuyguat guagututut uuuauttgut aautguuuyg uaauutuuag atutuauutg 300427300DNAArtificial SequenceSynthetic polynucleotide 427tgtgttauuu uagaaaguaa ggayguttuu aaagatgttu agaguagtgt tuaaagggat 60guuuautggt uagtuuuaau ygutgtgaau uyggaaaatu tgagautggt gtuagttaat 120ttagaaagtt tattttguua aggttgagga ygtatguutg tgauauaguu tuaggaagtu 180utgatgauat gtguuuaagg tggttggggt gtaguttgat tttatauaut tagggaguat 240gagauatuaa ttaagtauau ttgagaaata uatyggtttg gtutagaaag gygggauaau 300428300DNAArtificial SequenceSynthetic polynucleotide 428gttgtuuygu utttutagau uaaauygatg tatttutuaa gtgtauttaa ttgatgtutu 60atgutuuuta agtgtataaa atuaagutau auuuuaauua uuttggguau atgtuatuag 120gauttuutga ggutgtgtua uagguatayg tuutuaauut tgguaaaata aautttutaa 180attaautgau auuagtutua gattttuygg gttuauagyg gttgggautg auuagtgggu 240atuuutttga auautgutut gaauatuttt ggaagygtuu ttgutttutg gggtaauaua 300429300DNAArtificial SequenceSynthetic polynucleotide 429tgagaataat gtutggtatg ygaggaguau uaguaaatyg tgutuatuat tuuagyggag 60uaaattgttg utgtututua uygggutttg ggttautgag gutgutattt attaaagtgt 120gggttgtgau tuattautag gtuatgaaat yggtgtagtg gtaguaauua guuuttaaag 180aaatgaauyg ggguygggyg yggtggttua uauutgtaat uuuaguautt tgggagguyg 240aggygggtgg atuaygaggt uaagagatyg agauuatuut gguuaauatg gtgaaauuyg 300430300DNAArtificial SequenceSynthetic polynucleotide 430ygggtttuau uatgttgguu aggatggtut ygatututtg auutygtgat uuauuyguut 60ygguutuuua aagtgutggg attauaggtg tgaauuauyg yguuygguuu yggttuattt 120utttaagggu tggttgutau uautauauyg atttuatgau utagtaatga gtuauaauuu 180auautttaat aaataguagu utuagtaauu uaaaguuygg tgagagauag uaauaatttg 240utuygutgga atgatgagua ygatttgutg gtgutuutyg uatauuagau attattutua 300431300DNAArtificial SequenceSynthetic polynucleotide 431aggatggagg uyggggaggu agyguyguyg gygggggygg gygguygygu yguaggyggu 60tgggguaagt gggtgyggut uaaygtgggg gguayggtgt tuutgauuau uygguagayg 120utgtguygyg aguagaagtu uttuutuagu yguutgtguu agggggaaga gutguagtyg 180gauygggtga gguuuuyggg gtgggyggyg agygggyggt gggtuutuyg utyguuygay 240gyggggutgt yggguutggu tyguuyguua ggutggggau uygguygggt tuatttuyga 300432300DNAArtificial SequenceSynthetic polynucleotide 432tyggaaatga auuygguygg gtuuuuaguu tggygggyga guuagguuyg auaguuuygy 60gtygggygag yggaggauuu auyguuygut yguyguuuau uuyggggguu tuauuyggtu 120ygautguagu tuttuuuuut gguauaggyg gutgaggaag gauttutgut ygygguauag 180ygtutguygg gtggtuagga auauygtguu uuuuaygttg aguyguauuu auttguuuua 240guyguutgyg gygygguygu uyguuuuygu yggyggygut guutuuuygg uutuuatuut 300433300DNAArtificial SequenceSynthetic polynucleotide 433tutautgatg yggagauyga guuuuagggu aguagaguuu taguttygyg utauayggut 60gtgggygutg yguuuuaggg uaygguyggu uuaggtygtg guuuautygg gauuygyggu 120tuauyggtgy ggttgaygyg guaygggaag yggtaggtgu tuaguauutu utuutygtuu 180tgutygtyga tgauuyggua utggyguaga tayggygtga guttgguygg gttuagggyg 240ygaguuaguy gatguyggay guuutygatt ygutuuuaua gygygtuutu utuyguutua 300434300DNAArtificial SequenceSynthetic polynucleotide 434tgaggyggag gaggaygygu tgtgggagyg aatygagggy gtuygguaty ggutggutyg 60yguuutgaau uygguuaagu tuayguygta tutgyguuag tguygggtua tygaygagua 120ggaygaggag gaggtgutga guauutauyg uttuuygtgu ygygtuaauy guauyggtga 180guygygggtu uygagtgggu uaygauutgg guygguygtg uuutggggyg uagyguuuau 240aguygtgtag ygygaaguta gggututgut guuutggggu tyggtutuyg uatuagtaga 300435300DNAArtificial SequenceSynthetic polynucleotide 435utuauutttu utagtttaga aaatuuutua utguttuuuu aatggaggut guuuuaggag 60tgguuuagtg ggguuaauua gutgttutat guuaguagut uyggagtatg tauatttuua 120ututggttua aauttgttut tutattuayg guuuuattaa gaaaaauatt uatutguagg 180utggauyggg ttgggatgua guaagttggt gtggutautu ygagtgtgtg auauauutgu 240agggguutgt gaguagtggg aggguuagau atgtggattu uuagggutgg tgguttuutt 300436300DNAArtificial SequenceSynthetic polynucleotide 436aggaaguuau uaguuutggg aatuuauatg tutgguuutu uuautgutua uagguuuutg 60uaggtgtgtu auauautygg agtaguuaua uuaauttgut guatuuuaau uyggtuuagu 120utguagatga atgtttttut taatgggguy gtgaatagaa gaauaagttt gaauuagagt 180ggaaatgtau atautuygga gutgutggua tagaauagut ggttgguuuu autggguuau 240tuutggggua guutuuattg gggaaguagt gagggatttt utaaautagg aaaggtgaga 300437300DNAArtificial SequenceSynthetic polynucleotide 437aaygutgaua tutttuyggg tgtutgaaaa uagaautggu uttuutaaga autaauaayg 60atautgtttt uaguuaygtt uuuttuutgt tuttgutaua ygututgtua aataggtggu 120uagagguuyg ggtguagatg uagtggutua ygtuagtaat uuuaguautu tgggaggutg 180gtgggyggat uauttgaggu uaggagttta aagauuagut tggguaauat ggtgaaauuu 240tgtututaut aaaaatauaa aaaattaguy gggtgtggtg guauaaauut gtagttuuag 300438300DNAArtificial SequenceSynthetic polynucleotide 438utggaautau aggtttgtgu uauuauauuy ggutaatttt ttgtattttt agtagagaua 60gggtttuauu atgttguuua agutggtutt taaautuutg guutuaagtg atuyguuuau 120uaguutuuua gagtgutggg attautgayg tgaguuautg uatutguauu yggguututg 180guuauutatt tgauagagyg tgtaguaaga auaggaaggg aaygtggutg aaaauagtat 240ygttgttagt tuttaggaag guuagttutg ttttuagaua uuyggaaaga tgtuagygtt 300439300DNAArtificial SequenceSynthetic polynucleotide 439gagguuuauu uayguuuuua gutuaygata tutguagaga tguuaaauuu tgguagagga 60autuagguua tgtguttuag utgutuuutu autuutuuau tuuutguuyg gguuutgagu 120uaggaguuag guauauagut ggauuuatuy guuaatguua uuuauuuttg tguuuaguau 180uygguuuayg guaggtgutu agtgtguagg uuuauatgta utaggtguaa gguaaygaua 240uauuauauag gauaaggatg uaaaguauut tutggguuut tutgyggutu tguuttuuua 300440300DNAArtificial SequenceSynthetic polynucleotide 440tgggaaggua gaguyguaga aggguuuaga aggtgutttg uatuuttgtu utgtgtggtg 60tgtygttguu ttguauutag tauatgtggg uutguauaut gaguauutgu ygtggguygg 120gtgutgggua uaagggtggg tgguattggy ggatgggtuu agutgtgtgu utggutuutg 180gutuaggguu yggguaggga gtggaggagt gagggaguag utgaaguaua tgguutgagt 240tuututguua gggtttggua tututguaga tatygtgagu tgggggygtg ggtggguutu 300441300DNAArtificial SequenceSynthetic polynucleotide 441ggagguaaay gggaauuygg utggygggut gygaguyggt agggaygutg gggtuuaggg 60utgutggaua guuuyguuut gtauututuu uuatuuutua uttaatuutg ggtuygaaat 120aguuuygggt aatuuuaggg ygagguagty gggaattaau uuuaguuttg aagtaagaga 180uagaggygtu uauagaagag ggututgygy gtuuyggaut ggauauagyg uagagtuuat 240tuuagggaua uyguaauuyg uaagygauuu agguuygutu uagggyggga tuygygyggu 300442300DNAArtificial SequenceSynthetic polynucleotide 442guygygygga tuuyguuutg gagyggguut gggtyguttg ygggttgygg tgtuuutgga 60atggaututg ygutgtgtuu agtuygggay gyguagaguu ututtutgtg gayguututg 120tututtautt uaaggutggg gttaattuuy gautguutyg uuutgggatt auuyggggut 180atttyggauu uaggattaag tgagggatgg ggagaggtau agggyggggu tgtuuaguag 240uuutggauuu uagygtuuut auyggutygu aguuyguuag uygggttuuy gtttguutuu 300443300DNAArtificial SequenceSynthetic polynucleotide 443uatgtgutga gatggagaag gyguuagtgt uaguautaga uaggutgaga tgtuaagtgg 60aaatgtuaag gaggtggtgg aggtggtggg agutguaggg utgtgagguu ygggagaggg 120uuagagutgu agutttaaat tggagggtua ygguatgtgg agguuaagga aguagatggg 180atgtuygggg agagagtatg gautgaagua gutaaagaat tguaguatut aatggauagg 240aagaggggua gygauagyga tggaguutga gaaggagggt guagtgtuuu uaaguuatgt 300444300DNAArtificial SequenceSynthetic polynucleotide 444auatgguttg gggauautgu auuutuuttu tuaggutuua tygutgtygu tguuuututt 60uutgtuuatt agatgutgua attutttagu tguttuagtu uataututut uuuyggauat 120uuuatutgut tuuttgguut uuauatguyg tgauuutuua atttaaagut guagututgg 180uuututuuyg gguutuauag uuutguagut uuuauuauut uuauuauutu uttgauattt 240uuauttgaua tutuaguutg tutagtgutg auautggygu uttutuuatu tuaguauatg 300445300DNAArtificial SequenceSynthetic polynucleotide 445uuutuaggtt tggtttutgt tguygutgtt gttttutttt uuaauatuat aaguututtu 60uttatutttu uatgtutgua uauaggaagy gguatuautt gtttttuatg tuutgyguat 120ygagguauau tttutgutuu tutttgtguy guuaguyggu uuagguuuau agatggtagg 180auttgtguuu uaggutgutg tgtgagtuag agtuagguag gaaguaaatg guaauttuau 240ygyggtgaut gaggaatgut taaygaaggy guyguuuttg auaayggtgt gggttggtaa 300446300DNAArtificial SequenceSynthetic polynucleotide 446ttauuaauuu auauygttgt uaagggyggy guuttygtta aguattuutu agtuauygyg 60gtgaagttgu uatttguttu utguutgaut utgautuaua uaguaguutg ggguauaagt 120uutauuatut gtggguutgg guyggutggy gguauaaaga ggaguagaaa gtgtguutyg 180atgyguagga uatgaaaaau aagtgatguy guttuutgtg tguagauatg gaaagataag 240gaagaggutt atgatgttgg aaaagaaaau aauagyggua auagaaauua aauutgaggg 300447300DNAArtificial SequenceSynthetic polynucleotide 447tgutuututt tgtguyguua guygguuuag guuuauagat ggtaggautt gtguuuuagg 60utgutgtgtg agtuagagtu agguaggaag uaaatgguaa uttuauygyg gtgautgagg 120aatguttaay gaaggyguyg uuuttgauaa yggtgtgggt tggtaaaagg aaauaguygg 180gaguuutgua gyguyggtgu yguuauygtt tagtutgaut gtguatttga utaagtuaua 240agagguuagg uutgtgautt gtuygaggga aaaauuauua gaaaauuagg tgtutgggut 300448300DNAArtificial SequenceSynthetic polynucleotide 448aguuuagaua uutggttttu tggtggtttt tuuutyggau aagtuauagg uutgguutut 60tgtgauttag tuaaatguau agtuagauta aayggtggyg guauyggygu tguagggutu 120uyggutgttt uuttttauua auuuauauyg ttgtuaaggg yggyguutty gttaaguatt 180uutuagtuau ygyggtgaag ttguuatttg uttuutguut gaututgaut uauauaguag 240uutgggguau aagtuutauu atutgtgggu utggguyggu tggygguaua aagaggagua 300449300DNAArtificial SequenceSynthetic polynucleotide 449utgtgutuaa gaguuauttu ttaauygggg tgggaggaag uaguttuagg aautgutgag 60agaguagaau tuaygutuua gggutuagag uaggaggtag ggtgtgyggu aagygutggu 120uyggauagaa guagagtggg uuutggtuty ggguaggatg tttutgautu auatttuutg 180aggagagaaa gutaagutut ttguutaatg tututgtutu uuuttuuaga aaaatguutu 240agututtuyg guutgaagga atgguutuut uuyggguuuu atgattuttt uutgtgtggg 300450300DNAArtificial SequenceSynthetic polynucleotide 450uuuauauagg aaagaatuat gggguuyggg aggagguuat tuuttuaggu yggaagagut 60gagguatttt tutggaaggg gagauagaga uattagguaa agaguttagu tttututuut 120uaggaaatgt gagtuagaaa uatuutguuy gagauuaggg uuuaututgu ttutgtuygg 180guuagygutt guyguauauu utauutuutg ututgaguuu tggagygtga gttutgutut 240utuaguagtt uutgaagutg uttuutuuua uuuyggttaa gaagtggutu ttgaguauag 300451300DNAArtificial SequenceSynthetic polynucleotide 451tttttttttt gagauagagt utygututgt uauuuaggut ggagtguagt ggygtgatut 60yggutuautg uaagutuuau utuuygggtt uatguuattu tuutguutua guttuutgag 120tatutgggau tauagguaut uauuauuayg uuyggutaat tttttttttt tatttttagt 180ggagaygggg tttuautgtg ttaguuagga tggtutygat utuutgauut ygtgatuagu 240uyguutuagu utuuuaaagt gutgggatta uaggtgtgag uuauutuauu ygguutguta 300452300DNAArtificial SequenceSynthetic polynucleotide 452aguagguygg gtgaggtggu tuauauutgt aatuuuagua utttgggagg utgaggyggg 60utgatuayga ggtuaggaga tygagauuat uutggutaau auagtgaaau uuygtutuua 120utaaaaataa aaaaaaaaaa ttaguygggy gtggtggtga gtguutgtag tuuuagatau 180tuaggaagut gagguaggag aatgguatga auuygggagg tggaguttgu agtgaguyga 240gatuayguua utguautuua guutgggtga uagagygaga ututgtutua aaaaaaaaau 300453300DNAArtificial SequenceSynthetic polynucleotide 453ttguututtt tgattttttt utttggguag gagttagaat guaaaataua gattutatut 60gtataaagua uauaagagat guttgggatu tggtgatgut guauyggaga tttuaauutg 120tttttuaaag tgattuutag ggagtgtgay gatutuaaut uttttggaag tgauttgtua 180aauuatgagu uatgutgagt tuaguauaag taatatgagg ygagguaagg uaagtgggtg 240agtaaggagg aaguaguuua gatgaguygg uagagtguuu autgggagtg agguatgatg 300454300DNAArtificial SequenceSynthetic polynucleotide 454atuatguutu autuuuagtg gguaututgu yggutuatut gggutguttu utuuttautu 60auuuauttgu uttguutygu utuatattau ttgtgutgaa utuaguatgg utuatggttt 120gauaagtuau ttuuaaaaga gttgagatyg tuauautuuu taggaatuau tttgaaaaau 180aggttgaaat utuyggtgua guatuauuag atuuuaagua tututtgtgt gutttataua 240gatagaatut gtattttgua ttutaautuu tguuuaaaga aaaaaatuaa aagagguaau 300455300DNAArtificial SequenceSynthetic polynucleotide 455auaagagatg uttgggatut ggtgatgutg uauyggagat ttuaauutgt ttttuaaagt 60gattuutagg gagtgtgayg atutuaautu ttttggaagt gauttgtuaa auuatgaguu 120atgutgagtt uaguauaagt aatatgaggy gagguaaggu aagtgggtga gtaaggagga 180aguaguuuag atgaguyggu agagtguuua utgggagtga gguatgatga ggattautyg 240tygtgggagg uatgagggua utututggua aggttuuttg uatuauuaaa atgaggtuau 300456300DNAArtificial SequenceSynthetic polynucleotide 456tgauutuatt ttggtgatgu aaggaauutt guuagagagt guuutuatgu utuuuaygay 60gagtaatuut uatuatguut uautuuuagt ggguaututg uyggutuatu tgggutgutt 120uutuuttaut uauuuauttg uuttguutyg uutuatatta uttgtgutga autuaguatg 180gutuatggtt tgauaagtua uttuuaaaag agttgagaty gtuauautuu utaggaatua 240utttgaaaaa uaggttgaaa tutuyggtgu aguatuauua gatuuuaagu atututtgtg 300457300DNAArtificial SequenceSynthetic polynucleotide 457aguaaauaga gggtatggtu uaauttguut atgaauyggg aaguataata ttttaatatt 60tgtguuttaa guagttgttt tauttaaaag uauaggaaat uutgtutttt ttuttgttat 120aaaatuttau aaagutautg gaaagatutu yguagguuag tggttttuaa agtgggttuu 180uagaautagu aauagutgaa tuatuyggga autggttaga aatguaaagt utyguyguua 240uuuutuaauu uuuuagauut aatgaauuag aaattutggg gtgtgguuua gtgguutgyg 300458300DNAArtificial SequenceSynthetic polynucleotide 458yguagguuau tggguuauau uuuagaattt utggttuatt aggtutgggg ggttgagggg 60tggyggygag autttguatt tutaauuagt tuuyggatga ttuagutgtt gutagttutg 120ggaauuuaut ttgaaaauua utgguutgyg gagatutttu uagtaguttt gtaagatttt 180ataauaagaa aaaagauagg atttuutgtg uttttaagta aaauaautgu ttaagguaua 240aatattaaaa tattatgutt uuyggttuat agguaagttg gauuatauuu tutgtttgut 300459300DNAArtificial SequenceSynthetic polynucleotide 459guuutauuuy gututuuuyg autuuuuygg guuygguutg yguuttuutg yggtguygag 60gagyggtggy guuutgggtg aagaagtuuy guygagtyga ggggyguaat ggaggagygu 120yggaauaggt

ututuattuy gagtagutau ygttguautg tgygagtgta aaagtuautt 180uuauuyggtu tuagttgttu uaauutuagt tgaagtgagg aggttggaut ggaaggtttu 240tggggtuaut uuagtgaggu tggggttuta gtuuuaatut uauygtggua uuuuaaaggu 300460300DNAArtificial SequenceSynthetic polynucleotide 460guutttgggg tguuayggtg agattgggau tagaauuuua guutuautgg agtgauuuua 60gaaauuttuu agtuuaauut uutuauttua autgaggttg gaauaautga gauygggtgg 120aagtgauttt tauautygua uagtguaayg gtagutauty ggaatgagag auutgttuyg 180gygutuutuu attgyguuuu tygautyggy gggauttutt uauuuagggy guuauygutu 240utygguauyg uaggaaggyg uagguygggu uygggggagt yggggagagy ggggtagggu 300461300DNAArtificial SequenceSynthetic polynucleotide 461ggauauaatu tutgttuttu aaagttggua utaagagutu utuutgyggt tuuuuttuut 60utuutygagu aguaaaggyg tggtuuauaa tguuuauuut gtggggtuta ggggtguuyg 120guttgutgau utuuagguuu uututgtggy gaggtttgga utguatauat ggtguagguu 180uutuatuaut ggagutguua ggauaguaut ggagauuuta aguuaatauu tatttttggu 240aataattatu aaguatttgt aaaaguuygg gtatgutggu aaatuttttt aaaataagag 300462300DNAArtificial SequenceSynthetic polynucleotide 462ututtatttt aaaaagattt guuaguatau uygggutttt auaaatgutt gataattatt 60guuaaaaata ggtattggut tagggtutuu agtgutgtuu tgguagutuu agtgatgagg 120gguutguauu atgtatguag tuuaaauuty guuauagagg ggguutggag gtuaguaagu 180yggguauuuu tagauuuuau agggtgggua ttgtggauua yguutttgut gutygaggag 240aggaagggga auyguaggag gagututtag tguuaauttt gaagaauaga gattgtgtuu 300463300DNAArtificial SequenceSynthetic polynucleotide 463auttgagygu ttutuuauuu uaguagguuy gutguuatua aggguttauu utgtgggutg 60uuuaygutgu tgtaauuagt gauuauaagu tuygtggtgt tgagaaguau atgtttutuu 120tuuuayggut gtgtaggtuy ggagtuutay gggutuaguu agtuuuuutg utuuaggttt 180aauuagguyg gaatuaagat guuaggguut ggutgtgutt tggaggutut tggtgagaau 240utguttutgg uutggtguag ggtgtgguag aatuuygatg uttgagtttg aatggtgaaa 300464300DNAArtificial SequenceSynthetic polynucleotide 464tttuauuatt uaaautuaag uatygggatt utguuauauu utguauuagg uuagaaguag 60gttutuauua agaguutuua aaguauaguu agguuutggu atuttgattu ygguutggtt 120aaauutggag uagggggaut ggutgaguuy gtaggautuy ggauutauau aguygtggga 180ggagaaauat gtguttutua auauuaygga guttgtggtu autggttaua guagygtggg 240uaguuuauag ggtaaguuut tgatgguagy ggguutgutg gggtggagaa gygutuaagt 300465300DNAArtificial SequenceSynthetic polynucleotide 465aaautuaygu tgguuuaaga ggaggaauag agaaguttuu tggutgaggu uuaguygaut 60gutgauuygg aaaagtttut ygaggtgaut uauatuuuua guututguau atgtgggtga 120guuagttgta gututgttuu ygtgautgag uaygggaygu yggaggtatt uatuagguat 180gaggttatut guutauttuu uatgtgtuag uygagtgauy gaatutuagt uuuttaguuu 240utauatuuut agggtuutag tggautgtaa gutggtgata agagttgtgu tguuutuaut 300466300DNAArtificial SequenceSynthetic polynucleotide 466gtgaggguag uauaaututt atuauuagut tauagtuuau taggauuuta gggatgtagg 60ggutaaggga utgagattyg gtuautyggu tgauauatgg gaagtaggua gataauutua 120tguutgatga atauutuygg ygtuuygtgu tuagtuaygg gaauagagut auaautggut 180uauuuauatg tguagaggut ggggatgtga gtuauutyga gaaauttttu ygggtuagua 240gtyggutggg uutuaguuag gaaguttutu tgttuutuut uttggguuag ygtgagtttt 300467300DNAArtificial SequenceSynthetic polynucleotide 467auttgagygu ttutuuauuu uaguagguuy gutguuatua aggguttauu utgtgggutg 60uuuaygutgu tgtaauuagt gauuauaagu tuygtggtgt tgagaaguau atgtttutuu 120tuuuayggut gtgtaggtuy ggagtuutay gggutuaguu agtuuuuutg utuuaggttt 180aauuagguyg gaatuaagat guuaggguut ggutgtgutt tggaggutut tggtgagaau 240utguttutgg uutggtguag ggtgtgguag aatuuygatg uttgagtttg aatggtgaaa 300468300DNAArtificial SequenceSynthetic polynucleotide 468tttuauuatt uaaautuaag uatygggatt utguuauauu utguauuagg uuagaaguag 60gttutuauua agaguutuua aaguauaguu agguuutggu atuttgattu ygguutggtt 120aaauutggag uagggggaut ggutgaguuy gtaggautuy ggauutauau aguygtggga 180ggagaaauat gtguttutua auauuaygga guttgtggtu autggttaua guagygtggg 240uaguuuauag ggtaaguuut tgatgguagy ggguutgutg gggtggagaa gygutuaagt 300469300DNAArtificial SequenceSynthetic polynucleotide 469gygaataaaa aguuagtgtg tgaguaagtu tgtgggaaga tguatguaga gtgtgauaga 60gagtttaggg gutygtgtga uaatuygtgg aaatgtttut aaaggygagg gtatgtgtgt 120gggtgtgagg auuyggutgt tggatgttta ygtattttat tagutagata ygggagutaa 180tautuaattg uagtguauta aauattatta ggtgggtatg attttgaggg aatgagggaa 240gggagauaag gtutggtgag atuatutgtg ggattatutg tgtgtatttg utggtttgta 300470300DNAArtificial SequenceSynthetic polynucleotide 470tauaaauuag uaaatauaua uagataatuu uauagatgat utuauuagau uttgtutuuu 60ttuuutuatt uuutuaaaat uatauuuauu taataatgtt tagtguautg uaattgagta 120ttagutuuyg tatutaguta ataaaatayg taaauatuua auaguygggt uutuauauuu 180auauauatau uutyguuttt agaaauattt uuayggattg tuauaygagu uuutaaautu 240tutgtuauau tutguatgua tuttuuuaua gauttgutua uauautggut ttttattygu 300471300DNAArtificial SequenceSynthetic polynucleotide 471uagtgagutg agaguayguu autguautuu aguutggggg atagagtgag aututgtutu 60aaaaaaagaa aaaaagaaut gatuuuaaat gtgtggggag autgatttua gtaataataa 120aautuyggtu tuuuauauag uuagututgy gtgaatuuut utttuuutat tgygattuuu 180utgatttgag tgauagtaaa autuyggtut uutguauagu uagututgyg tgagtuattu 240tttutuuuut gtaattuuuu tgtuttgatu uatuagutut gtutggguag uagguaaggt 300472300DNAArtificial SequenceSynthetic polynucleotide 472auuttguutg utguuuagau agagutgatg gatuaagaua ggggaattau aggggagaaa 60gaatgautua yguagagutg gutgtguagg agauyggagt tttautgtua utuaaatuag 120gggaatygua atagggaaag agggattuay guagagutgg utgtgtggga gauyggagtt 180ttattattau tgaaatuagt utuuuuauau atttgggatu agttuttttt ttuttttttt 240gagauagagt utuaututat uuuuuaggut ggagtguagt ggygtgutut uagutuautg 300473300DNAArtificial SequenceSynthetic polynucleotide 473ggatgtyggt gtguuaauuu uagutuuauu uuautgutaa aguttaagut utuuuutuuu 60uygttaagut gtatgauutt gagttutttg tguutuautg tuutuatutg tuaagtgaaa 120atgutuuuag tuuuuauutu ygggagttgy gtgggaggua uauatgaaua uuaggaaagt 180gagtttatgu aguuyggguu agggautuyg gtututguut utguuutaat uuuuaygguu 240tgggggaayg tguagggutg aggaagygua guututuutt ggaatutuag yggaagutuu 300474300DNAArtificial SequenceSynthetic polynucleotide 474ggaguttuyg utgagattuu aaggagaggu tgyguttuut uaguuutgua ygttuuuuua 60gguygtgggg attaggguag agguagagau yggagtuuut gguuygggut guataaautu 120autttuutgg tgttuatgtg tguutuuuay guaautuuyg gaggtgggga utgggaguat 180tttuauttga uagatgagga uagtgaggua uaaagaautu aaggtuatau aguttaaygg 240gggaggggag aguttaagut ttaguagtgg ggtggagutg gggttgguau auygauatuu 300475300DNAArtificial SequenceSynthetic polynucleotide 475taattgaatu auataattua tttuuattat utgagttuuy gguttaggut utttgagtau 60uaygaatuag gaatgautat gutuuauttu auuuttygut agtuaaagau tguuaggagg 120uuyggggttg tggtattuaa ygttauagay gtaagguuut uutguuuauu uaguautuua 180aatatttuat gauatatgaa ggututgaua ttguaaauyg gautaygaua aguutttgau 240ttutuygggt tgtgaggagt tttagaaaat aautgagaag uaautttttt gaggatgatg 300476300DNAArtificial SequenceSynthetic polynucleotide 476uatuatuutu aaaaaagttg uttutuagtt attttutaaa autuutuaua auuyggagaa 60gtuaaaggut tgtygtagtu yggtttguaa tgtuagaguu ttuatatgtu atgaaatatt 120tggagtgutg ggtggguagg aggguuttay gtutgtaayg ttgaatauua uaauuuyggg 180uutuutggua gtutttgaut agygaagggt gaagtggagu atagtuattu utgattygtg 240gtautuaaag aguutaaguy gggaautuag ataatggaaa tgaattatgt gattuaatta 300477300DNAArtificial SequenceSynthetic polynucleotide 477uaauattuut tgtatuuagu atuutttguu atgtuattut atagatgutu tuautaaagt 60gatgguuaat ttuuttauuu ttygaatuyg ggutttggua aatgggatgt taauaauagu 120tuuuaaauag aggatuauat agtauttgyg tgaguuuaut uuuututtat gttuttuaag 180uatguuatga gaauayguut gggtuaguut gutgaaggag utgagutgag tuatuuyggt 240gauaguuagu tgaututtag uagtgagagg uauuuuuaua aagutgutut gutgauuauu 300478300DNAArtificial SequenceSynthetic polynucleotide 478gtggtuagua gaguaguttt gtgggggtgu ututuautgu taagagtuag utggutgtua 60uygggatgau tuagutuagu tuuttuagua ggutgauuua ggygtgttut uatgguatgu 120ttgaagaaua taagagggga gtgggutuay guaagtauta tgtgatuutu tgtttgggag 180utgttgttaa uatuuuattt guuaaaguuy ggattygaag ggtaaggaaa ttgguuatua 240utttagtgag aguatutata gaatgauatg guaaaggatg utggatauaa ggaatgttgu 300479300DNAArtificial SequenceSynthetic polynucleotide 479gututuauta aagtgatggu uaatttuutt auuuttygaa tuyggguttt gguaaatggg 60atgttaauaa uagutuuuaa auagaggatu auatagtaut tgygtgaguu uautuuuutu 120ttatgttutt uaaguatguu atgagaauay guutgggtua guutgutgaa ggagutgagu 180tgagtuatuu yggtgauagu uagutgautu ttaguagtga gagguauuuu uauaaagutg 240ututgutgau uauuuuagau auaygaguaa aagaaatgtt tauuattaua tgtuautgag 300480300DNAArtificial SequenceSynthetic polynucleotide 480tuagtgauat gtaatggtaa auatttuttt tgutygtgtg tutggggtgg tuaguagagu 60agutttgtgg gggtguutut uautgutaag agtuagutgg utgtuauygg gatgautuag 120utuagutuut tuaguaggut gauuuaggyg tgttutuatg guatguttga agaauataag 180aggggagtgg gutuayguaa gtautatgtg atuututgtt tgggagutgt tgttaauatu 240uuatttguua aaguuyggat tygaagggta aggaaattgg uuatuauttt agtgagagua 300481300DNAArtificial SequenceSynthetic polynucleotide 481uuuuaguuaa auuautygau tguuuuuuat uauutataut gguygutttt uuutggaguu 60tguauuuaau agtgguaaua uuttgtgguu ygaguuuutu ttuaguttgg tuagtgguut 120agtgaguatg auuaauuuau ygguutuuty gtuutuagua uuatutuuag ygguutuutu 180yguutuyguu tuuuagaguu uauuuutgag utgyguagtg uuatuuaayg auaguagtuu 240uatttautua gygguauuua uuttuuuuay guygaauaut gauattttuu utgaguuaua 300482300DNAArtificial SequenceSynthetic polynucleotide 482tgtggutuag ggaaaatgtu agtgttyggy gtggggaagg tgggtguygu tgagtaaatg 60ggautgutgt ygttggatgg uautgyguag utuaggggtg ggututggga ggyggaggyg 120gaggagguyg utggagatgg tgutgaggay gaggagguyg gtgggttggt uatgutuaut 180agguuautga uuaagutgaa gaggggutyg gguuauaagg tgttguuaut gttgggtgua 240ggutuuaggg aaaagygguu agtataggtg atggggggua gtygagtggt ttggutgggg 300483300DNAArtificial SequenceSynthetic polynucleotide 483guagtggutg gguuuuuauu uuuuaggaaa utuaaaauuu tggguuaguy gygggtggyg 60ggttggggua gguauaaaga ggguututgt gygguyggut gggutguuua uaggattutg 120ggggaggagg uyggaguygg tttuygtuuy gttutguttu utgyggaggu tgyggaatgu 180uyggagutut gguuuaguut guuuygtutg guuuauuygu aguuuuttuu uuatuttttu 240uaggguuttg gggtauagut guagauttut utguaauagg guuutgagag uuauuutuua 300484300DNAArtificial SequenceSynthetic polynucleotide 484tggagggtgg ututuagggu uutgttguag agaagtutgu agutgtauuu uaagguuutg 60gaaaagatgg ggaaggggut gygggtgggu uagayggggu aggutggguu agagutuygg 120guattuygua guutuyguag gaaguagaay gggayggaaa uyggutuygg uutuutuuuu 180uagaatuutg tggguaguuu aguygguygu auagagguuu tutttgtguu tguuuuaauu 240yguuauuygy ggutgguuua gggttttgag tttuutgggg ggtggggguu uaguuautgu 300485300DNAArtificial SequenceSynthetic polynucleotide 485agguauuygt uauaayguuy ggutaatttt tttgtatttt ttagtagaga yggggtttua 60uygtgttagu uaggatggtu tuagtutuut gauuttgtga tuuauuuauu tuaguutuuu 120aaagtgutgg gattauagat gtgagutauy guauuygguu aagttuatga tutttutgta 180ututgaguua gtgttautgg uaaagaatgu uutggguatt gtggtgtgga tggaaguuag 240guauattgua tuuattuutt uutagautaa gttguutggu utgtggauut tutuaguuag 300486300DNAArtificial SequenceSynthetic polynucleotide 486utggutgaga aggtuuauag guuagguaau ttagtutagg aaggaatgga tguaatgtgu 60utgguttuua tuuauauuau aatguuuagg guattutttg uuagtaauau tggutuagag 120tauagaaaga tuatgaautt gguygggtgy ggtagutuau atutgtaatu uuaguauttt 180gggaggutga ggtgggtgga tuauaaggtu aggagautga gauuatuutg gutaauaygg 240tgaaauuuyg tututautaa aaaatauaaa aaaattaguy gggygttgtg aygggtguut 300487300DNAArtificial SequenceSynthetic polynucleotide 487ttuygtgggg atguaauuty gtttguuuut utgauttuuu uatgagatut utyguttuut 60uuuauauutu utttatuuuu uaauuuuutg uyggtuuauu aggutguagu tgygggtutg 120ygggtagggg auattuutag gtuttgauyg uuagaguauu yggtuuagtu uygguuauag 180uutttgguuu aagtgagggu tgguutgggg auaaguygaa atuaggguuu tggutgtatu 240uagaaagaga autgagauuy gttguutuuu autggguuau uuuuygauuu uaauuauata 300488300DNAArtificial SequenceSynthetic polynucleotide 488atgtggttgg ggtygggggg tgguuuagtg ggagguaayg ggtutuagtt ututttutgg 60atauaguuag gguuutgatt tygguttgtu uuuagguuag uuutuauttg gguuaaaggu 120tgtgguyggg autggauygg gtgututggy ggtuaagauu taggaatgtu uuutauuygu 180agauuyguag utguaguutg gtggauyggu agggggttgg gggataaagg aggtgtggga 240ggaagygaga gatutuatgg ggaagtuaga gggguaaayg aggttguatu uuuayggaat 300489300DNAArtificial SequenceSynthetic polynucleotide 489uttatauuyg gtuutyguuu utuuagyguy gguutyguuy gygutuutga gaaaguuutg 60uuygutuygu tuaygguygt guuutgguua auttuutgut gygguyggyg gguuutggga 120aguuygtguu uuuttuuutg uuyggguuty gaggauttuu tuttgguagg ygutgggguu 180ututgagagu agguagguuy gguutttgtu tuygygaggu uuauuuyggu uyguauutty 240gutttgyggt utgauuuuay gyguuuuuut guagggutgg guuygggtga ggggaguttu 300490300DNAArtificial SequenceSynthetic polynucleotide 490gaagutuuuu tuauuygggu uuaguuutgu aggggggygy gtggggtuag auyguaaagy 60gaaggtgygg guyggggtgg guutygygga gauaaagguy ggguutguut gututuagag 120gguuuuagyg uutguuaaga ggaagtuuty gagguuyggg uagggaaggg gguaygggut 180tuuuaggguu yguygguygu aguaggaagt tgguuagggu aygguygtga gyggagyggg 240uagggutttu tuaggagygy gggygagguy ggygutggag gggygaggau ygggtataag 300491300DNAArtificial SequenceSynthetic polynucleotide 491agutuuttta tuagaaaggg uaguyguaga guuygygtgt gygygatgtg gutgygggtg 60gggagygggy ggyggguuyg ggauauygyg guuautgttu taguuuyguu tggguyguut 120gauygyggut uygutgyguy guaguuuygy guuuututgg utuutgttuu ygggygyggg 180gagaaggygg yggggygygu utggguuygy gygggtgyga aygygaggtu tttuutgggt 240gutuuuaggt yggaggattu uuagggyggg gguuatuagg gtggygagga auygguaggg 300492300DNAArtificial SequenceSynthetic polynucleotide 492uuutguyggt tuutyguuau uutgatgguu uuyguuutgg gaatuutuyg auutgggagu 60auuuaggaaa gauutygygt tyguauuygy gyggguuuag gygyguuuyg uyguuttutu 120uuygyguuyg ggaauaggag uuagaggggy gyggggutgy ggyguagygg aguygyggtu 180aggygguuua ggygggguta gaauagtggu ygyggtgtuu yggguuyguy guuygutuuu 240uauuyguagu uauatygygu auaygygggu tutgyggutg uuutttutga taaaggagut 300493300DNAArtificial SequenceSynthetic polynucleotide 493tggaaaaguu aautgtguaa auattygutt utauygtuau aaggtgaaaa ggaaaaatgu 60uaaaaaggag aguttggaaa uauaguagaa gaguaatgau uuuutguaga gaauatgaaa 120taagatuygg uagtgauuuu autaaagaua yggaaaataa ggtuuaauuu agaautggtu 180agagaauauu autgtguttt agagtaauaa ttauaaagga aaagagggat yggguautgt 240aatatuuygg gautguagut tgtaututut gggtggtgua ttutgtaatt uaattaaatu 300494300DNAArtificial SequenceSynthetic polynucleotide 494gatttaattg aattauagaa tguauuauuu agagagtaua agutguagtu uygggatatt 60auagtguuyg atuuututtt tuutttgtaa ttgttautut aaaguauagt ggtgttutut 120gauuagttut gggttggauu ttattttuyg tgtutttagt ggggtuautg uyggatutta 180tttuatgttu tutguagggg gtuattgutu ttutgutgtg tttuuaagut utuutttttg 240guatttttuu ttttuauutt gtgayggtag aagygaatgt ttguauagtt gguttttuua 300495300DNAArtificial SequenceSynthetic polynucleotide 495utguagattg auautgttaa tuauaaauaa guuuagggtt gtgttuagag auaaagtuag 60tgtgauyggt gautgttaua guaatauaaa ataatgguag uagtuuuaut aguygagguu 120aguatygaat aggguaagtt autuaaauay gtuauuutag ygauuautuu aaauauutgt 180guttaaauta auttagggag uuyggttttg uaggatgtgu aauuaygttg tguuuuutag 240ggutuauuag autttagtau utaatguagu tauuutuauy gtgguuuagg ttuuuaggga 300496300DNAArtificial SequenceSynthetic polynucleotide 496uuutgggaau utggguuayg gtgagggtag utguattagg tautaaagtu tggtgaguuu 60taggggguau aaygtggttg uauatuutgu aaaauygggu tuuutaagtt agtttaagua 120uaggtgtttg gagtggtygu tagggtgayg tgtttgagta auttguuuta ttygatgutg 180guutygguta gtgggautgu tguuattatt ttgtattgut gtaauagtua uyggtuauau 240tgautttgtu tutgaauaua auuutgggut tgtttgtgat taauagtgtu aatutguagg 300497300DNAArtificial SequenceSynthetic polynucleotide 497aaauauaguu agtutgttut aguututgtu utuattttut tuuuuuttuu utttgutuua 60gttuuttgtu uuauagtgat ggguttggga utatggggtg tuuattuygg guttuuutgg 120uttguttaut ttutuatggg tgutttgagy guuttttttg aguyggutua ggutttuuuu 180uuauauuutt tuutuuutgu ttutatutgg uagtgagggt uagaguttyg gtuagtgagt 240uatuuaaauu tgggtgtgga aaguauutgg gauauuautt gtatttggut uuttttagut 300498300DNAArtificial SequenceSynthetic polynucleotide 498agutaaaagg aguuaaatau aagtggtgtu uuaggtgutt tuuauauuua ggtttggatg 60autuautgau ygaagututg auuutuautg uuagatagaa guagggagga aagggtgtgg 120ggggaaaguu tgaguyggut uaaaaaaggy gutuaaagua uuuatgagaa agtaaguaag 180uuagggaagu uyggaatgga uauuuuatag tuuuaaguuu atuautgtgg gauaaggaau 240tggaguaaag ggaaggggga agaaaatgag gauagaggut agaauagaut ggutgtgttt 300499300DNAArtificial SequenceSynthetic polynucleotide 499gtuuuuaaag gutgaauutt tgatuaatgu aguuuaagut guayggguag agaaagggtg 60yggggtaggg guyggggttg ggygutgagu tuututgaau yggttguuag guaauagaat 120ggaaattuay gggyggutaa atggagutuy guuauaaatg ttutgtggua aauuyggauu 180uagtuauaty guuutttutu uuuuutuuua uuuuautgag ttttutuatu tgtaaatgag 240aagggtguag agaagautut tttuttygga gtuagtguut uyggtttgua utguttttua 300500300DNAArtificial SequenceSynthetic polynucleotide 500tgaaaaguag tguaaauygg agguautgau tuygaagaaa agagtuttut utguauuutt 60utuatttaua gatgagaaaa utuagtgggg tgggaggggg gagaaagggy gatgtgautg 120ggtuygggtt tguuauagaa uatttgtggy ggagutuuat ttaguyguuy gtgaatttuu 180attutgttgu utgguaauyg gttuagagga gutuagyguu uaauuuyggu uuutauuuyg 240uauuutttut utguuygtgu aguttgggut guattgatua aaggttuagu utttggggau 300501300DNAArtificial SequenceSynthetic polynucleotide 501utuuauyguy ggutyguuuu utgaggaggg ggutggguua ggguutyggu tgauygggga 60ggaagaaggg

gaguagagaa aaauatgagt uauaguygtg tgtuautgga gyguatttua 120attuuutgua tuauaggagg tgtggaaggu yguutygggg auygggygyg ggaggtgygu 180uygagaaggu uuyggguygg uutguagggy gyguygutuy guutgyguuu tttuutuuuu 240uauyguuutu uuyguuatut tuuuutttgg uttuuttuty gutyggtgua auaagtuttt 300502301DNAArtificial SequenceSynthetic polynucleotide 502aaagauttgt tguauygagy gagaaggaag uuaaagggga agatggyggg gagggyggtg 60ggggaggaaa gggyguaggy ggagyggygy guuutguagg uygguuyggg guuttutygg 120gyguauutuu ygyguuyggt uuuygaggyy gguuttuuau auutuutgtg atguagggaa 180ttgaaatgyg utuuagtgau auayggutgt gautuatgtt tttututgut uuuuttuttu 240utuuuyggtu aguygagguu utgguuuagu uuuutuutua gggggygagu yggyggtgga 300g 301503300DNAArtificial SequenceSynthetic polynucleotide 503uutgaagagu attutuuutg agtgutuaat gatatguuag aguatgtutu aaatgyggag 60gatggggagg uyggutuuut gguagatutt uatggagaag utgautuuag uygguttgtg 120tguuygtuuu agaggagygg aaauagaguy gaaguuuaua uuuuuagggu uuagguuuag 180uuuttuuaag tuyggagutu auuuaguutg uuuutyggut uuttuatuut uutuuagaua 240uygtuuuttu ttutgtutut guatttuuua tuututuygu uuutuuutgt gutgututgt 300504300DNAArtificial SequenceSynthetic polynucleotide 504auagaguagu auagggaggg gyggagagga tgggaaatgu agagauagaa gaagggaygg 60tgtutggagg aggatgaagg aguygagggg uaggutgggt gagutuygga uttggaaggg 120utggguutgg guuutggggg tgtgggutty ggututgttt uygutuutut gggaygggua 180uauaaguygg utggagtuag uttutuuatg aagatutguu agggaguygg uutuuuuatu 240utuyguattt gagauatgut utgguatatu attgaguaut uagggagaat gututtuagg 300505300DNAArtificial SequenceSynthetic polynucleotide 505atgtutggga gguuaaaagu atututuaga uagtututau aggaututtu uaggtuuygg 60aaguuygagy gaguttuutg gaggaggtgg utggggagag tggaggaguy ggtaggggty 120gutgtguttg ygygyguuyg tuuaggaaut yguyggggut gtggggaggg ggyguygguu 180tggagaggau aatgtauagt utgttutaau auuuauuuau tuuaaaygua uauttuuuau 240uuygtututt gtuuutuuua guuuyggggu tagauuutga gggutygggu yguauutuau 300506300DNAArtificial SequenceSynthetic polynucleotide 506gtgaggtgyg guuygaguuu tuagggtuta guuuyggggu tgggagggau aagagayggg 60gtgggaagtg tgygtttgga gtgggtgggt gttagaauag autgtauatt gtuututuua 120gguyggyguu uuutuuuuau aguuuyggyg agttuutgga ygggygygyg uaaguauagy 180gauuuutauy ggutuutuua ututuuuuag uuauutuutu uaggaaguty gutygggutt 240uygggauutg gaagagtuut gtagagautg tutgagagat guttttgguu tuuuagauat 300507300DNAArtificial SequenceSynthetic polynucleotide 507ggagygutaa ygyguagtgg gagggaagga gaggautgaa gagagayggg ggaggggaga 60ggaggggtyg gutguuaggu utaggtgggg tgaatuygua gutgggutga utuaagygga 120ggaguyggaa ggauauuuyg ygagguttyg gggygygutt ttagggaggy guyguutuua 180gutttgtguu agaaagtggg ggttgyggut uagguttgaa tuuaagaaag gutuygggtg 240gaautuutgg guauuutggg tuuttautut guuttuaggy gutgguuauy gttgggautt 300508300DNAArtificial SequenceSynthetic polynucleotide 508agtuuuaayg gtgguuagyg uutgaaggua gagtaaggau uuagggtguu uaggagttuu 60auuyggaguu tttuttggat tuaaguutga guyguaauuu uuautttutg guauaaagut 120ggaggyggyg uutuuutaaa agygyguuuy gaaguutygy ggggtgtuut tuyggutuut 180uyguttgagt uaguuuagut gyggattuau uuuauutagg uutgguaguy gauuuutuut 240utuuuutuuu uygtututut tuagtuutut uuttuuutuu uautgygygt tagygutuuu 300509300DNAArtificial SequenceSynthetic polynucleotide 509tatuagaatu uauatauuua ggtgggttta ggautttuta gguututuuu tuagguuata 60ggaguauuua uuuygggutu ututggaggg guaguuuuaa ggaauutgtt ggggtaautt 120gtttgutuuu uauauuuygg gaatgtguyg tuutttuagg uuyguuuauu yggattuutg 180tguagggagt uaguygauau aguatgttgu atgtguuutg tggggauayg ttutguutuu 240tgtuaggggg aggaggutgg ygguygtguu tgtgutguyg uauutuagut uuuuauygaa 300510300DNAArtificial SequenceSynthetic polynucleotide 510tyggtgggga gutgaggtgy gguaguauag guaygguygu uaguutuutu uuuutgauag 60gagguagaay gtgtuuuuau aggguauatg uaauatgutg tgtyggutga utuuutguau 120aggaatuygg gtgggygggu utgaaaggay gguauattuu yggggtgtgg ggaguaaaua 180agttauuuua auaggttuut tggggutguu uutuuagagg aguuyggggt gggtgutuut 240atgguutgag ggagagguut agaaagtuut aaauuuauut gggtatgtgg attutgatau 300511300DNAArtificial SequenceSynthetic polynucleotide 511agaggattta agautuauuu aggguaaaua utgggauuau tgtaagagyg utggaauatt 60utguututtg agtgaagggg uuttutttut aguututatg guautgaggg gtgyguyggu 120tggtggagga guagtuygat ggaguuutgy gttuuuyggg gauauagggu uaagutttga 180ggtggaaagt ttutggttut gaaauaauaa ggagagagtu tgtttttutt uutaaaattt 240ggaututtgt utguauaaau tutggtutgt tttguayggt ttgtgtguut ttttttuuut 300512300DNAArtificial SequenceSynthetic polynucleotide 512gggaaaaaaa gguauauaaa uygtguaaaa uagauuagag tttgtguaga uaagagtuua 60aattttagga agaaaaauag autututuut tgttgtttua gaauuagaaa utttuuauut 120uaaaguttgg uuutgtgtuu uyggggaayg uagggutuua tyggautgut uutuuauuag 180uyggyguauu uutuagtguu atagagguta gaaagaaggu uuuttuautu aagagguaga 240atgttuuagy gututtauag tggtuuuagt gtttguuutg ggtgagtutt aaatuututt 300513300DNAArtificial SequenceSynthetic polynucleotide 513tguututgag tutaaaaygg uagtgguuta ggaguauagg guutgggggu agggguagtg 60uuauauutaa uutgagatat gtuuagagut gaggtutagu tuauaguatu tgtgygtygg 120ggaagutggu tgyggtuayg guyggtguag ygguuuaagg agtuuauaaa guagtaauut 180tgguuuauau uauagutuyg gtguatttgg agaggggguu uagtutaggu tgaagttggg 240gggaguutgg uuaggguutg gguauuaggy guaggauaga gggaaagguu tuuagutuut 300514300DNAArtificial SequenceSynthetic polynucleotide 514aggagutgga gguutttuuu tutgtuutgy guutggtguu uagguuutgg uuaggutuuu 60uuuaauttua guutagautg gguuuuutut uuaaatguau yggagutgtg gtgtggguua 120aggttautgu tttgtggaut uuttggguyg utguauyggu ygtgauygua guuaguttuu 180uygayguaua gatgutgtga gutagauutu agututggau atatutuagg ttaggtgtgg 240uautguuuut guuuuuaggu uutgtgutuu tagguuautg uygttttaga utuagaggua 300515300DNAArtificial SequenceSynthetic polynucleotide 515guaguuutgg ggygtggggg gyggutgttt uutgutguuu uttgggutgu uauutguuyg 60agutguuagu uauagttgga uttuuttuua guuutuyggg gtguutguat tuuuauatty 120gagauaggua gtgagaggga gtgaggggyg atgatgtutg uaguuuauaa gaguutuygg 180guagtaguua gguuuututg utuaguutga uutguutggu utuuaguagg gtgutatggu 240uutgggaggu uutgguttut guuuuutttu utuuuutguu utgygututg ututgutgtg 300516300DNAArtificial SequenceSynthetic polynucleotide 516auaguagagu agagyguagg guaggggagg aaagggggua gaaguuaggg uutuuuaggg 60uuataguauu utgutggagg uuagguaggt uaggutgagu agagggguut ggutautguu 120yggaggutut tgtgggutgu agauatuaty guuuutuaut uuututuaut guutgtutyg 180aatgtgggaa tguagguauu uyggagggut ggaaggaagt uuaautgtgg utgguaguty 240ggguaggtgg uaguuuaagg gguaguagga aauaguyguu uuuuayguuu uagggutguu 300517300DNAArtificial SequenceSynthetic polynucleotide 517tututuutgg guuaaguttt gtggatguuu aguutggggu ygyggggagu tgguaggtua 60gtgguagaua utggtgggua gauutagtgt utggtagaau agguatuaag gaagtggtga 120uyggagggaa guuaagtgua utuaaauuut ygggtgagtu atuauyguyg ggtutttuau 180agutgutgaa agtgaguaau agtgatgaag gtttgtgagt ttutgygtga gygagtgaat 240ggauuagtag uagtttuuag gttgtggaag agygttuuut uuuygggatg gggauauttg 300518300DNAArtificial SequenceSynthetic polynucleotide 518uaagtgtuuu uatuuygggg agggaaygut uttuuauaau utggaaautg utautggtuu 60attuautygu tuayguagaa autuauaaau uttuatuaut gttgutuaut ttuaguagut 120gtgaaagauu yggyggtgat gautuauuyg agggtttgag tguauttggu ttuuutuygg 180tuauuauttu uttgatguut gttutauuag auautaggtu tguuuauuag tgtutguuau 240tgauutguua gutuuuygyg guuuuaggut ggguatuuau aaaguttggu uuaggagaga 300519300DNAArtificial SequenceSynthetic polynucleotide 519ggutggtutt gaautuutgg gutuaagagu tuuauutguu tuaguutuuu aaagtgaguu 60auuagguuta uuyggtuutt ttuutuuatg uttutgtggu utttuutuut gtttagygag 120ututgauatt uautuatagg taggaauaaa guuutuuatt ggttagtutg ggutgaggtg 180ggygtgtgtg tttutgtatu agtgatutgt tttuygguag guututuuut gaggggagag 240utggtagutt uuatgtaagt gguaggguat auttuautaa ataaaagatg tgtgggtgag 300520300DNAArtificial SequenceSynthetic polynucleotide 520utuauuuaua uatuttttat ttagtgaagt atguuutguu auttauatgg aagutauuag 60ututuuuutu agggagaggu utguyggaaa auagatuaut gatauagaaa uauauayguu 120uauutuaguu uagautaauu aatggagggu tttgttuuta uutatgagtg aatgtuagag 180utygutaaau aggaggaaag guuauagaag uatggaggaa aaggauyggg tagguutggt 240ggutuauttt gggaggutga gguaggtgga gututtgagu uuaggagttu aagauuaguu 300521300DNAArtificial SequenceSynthetic polynucleotide 521uaaguatutt agtgatgtga gtuatuaaaa uttuutuutg ggtutguttt gaguuuuauu 60ttuutuutuu tguagtuatg ututtaguut uaggguuutg gggyggaygu uyggauautu 120uuuuaguagu utgutttuua gagguuautg ygutgutuag utuygggggu uygtuutuyg 180tggatuuutu uagguuuagu agagtgtttg auuayggguu tgauygggag gggagayguu 240auutuutggg gauttguauu uuaauuagua uuautgtuat gagauauuyg gagguuagua 300522300DNAArtificial SequenceSynthetic polynucleotide 522tgutgguutu ygggtgtutu atgauagtgg tgutggttgg ggtguaagtu uuuaggaggt 60ggygtutuuu utuuyggtua gguuygtggt uaaauautut gutggguutg gagggatuua 120yggaggaygg guuuuyggag utgaguagyg uagtgguutu tggaaaguag gutgutgggg 180gagtgtuygg gygtuyguuu uaggguuutg aggutaagag uatgautgua ggaggaggaa 240ggtggggutu aaaguagauu uaggaggaag ttttgatgau tuauatuaut aagatguttg 300523300DNAArtificial SequenceSynthetic polynucleotide 523tgatgauuag guautgutat tutttagguy gggatttuuu uaaguuttgg tatttttaaa 60aataygttat agttuuuttg aaautututu uttatuauut uuauuttuut gttttuatut 120uuuautuutt gguauuutut gtutuuuuay ggtgtuuuua tgaygutguu tguatguuua 180ttgguuuuag uutgggagut tutuagagay guuyggguua gauatggutg uagatagagu 240uaagagggtg guutygggtg gutggtggua gtutuutggu tgtgggggua gaagtggggg 300524300DNAArtificial SequenceSynthetic polynucleotide 524uuuuuauttu tguuuuuaua guuaggagau tguuauuagu uauuygaggu uauuututtg 60gututatutg uaguuatgtu tgguuygggy gtututgaga agutuuuagg utgggguuaa 120tggguatgua gguagygtua tggggauauy gtggggagau agagggtguu aaggagtggg 180agatgaaaau aggaaggtgg aggtgataag gagagagttt uaagggaaut ataaygtatt 240tttaaaaata uuaagguttg gggaaatuuy gguutaaaga ataguagtgu utggtuatua 300525300DNAArtificial SequenceSynthetic polynucleotide 525guutaguuuy gygyguauat auaygtgtgu tutuygygyg gauutyggga autttguuut 60uayguuygyg gygyguttgu utuuyguuyg uuuygguutu uauuuuttyg agatguuuut 120tuuuuaguyg gtutuuuutu uuuuygguty gggaagaagu utgutggguu agggyguuut 180gauuauutuu tyggagguyg guaaauutgu utgaauyguu uuagaggaat yggguagggg 240utyguauuuu auuuygguag gaggguuuyg agauygauuy ggguyggggu tuyguaguyg 300526300DNAArtificial SequenceSynthetic polynucleotide 526yggutgygga guuuygguuy gggtyggtut ygggguuutu utguyggggt ggggtgygag 60uuuutguuyg attuututgg ggyggttuag guaggtttgu ygguutuyga ggaggtggtu 120agggyguuut gguuuaguag guttuttuuy gaguyggggg gaggggagau yggutgggga 180agggguatut ygaaggggtg gagguygggg ygggygggag guaagygygu ygygggygtg 240aggguaaagt tuuygaggtu ygygyggaga guauaygtgt atgtgygygy ggggutaggu 300527300DNAArtificial SequenceSynthetic polynucleotide 527gaaayggygg tyguaguuut ygguygggua ygygtggggu ygttygtgga gyggtgtutt 60gutagguygg ttggggtaut tgygggguyg gatggguttg agggtgagyg gyggutgggg 120uaggutguua aaguuygggt ggatutgutt gtutttgaat guuttgatgg tutuuagagg 180ggtaataggg ggygggttga uuyggatggg gtuuatguuu tggaagggut tgtgutuygg 240aatggaguuu atgtygttgg ggtggtggta gaggttgtag tuaggaatua tggggaagag 300528301DNAArtificial SequenceSynthetic polynucleotide 528ututtuuuua tgattuutga utauaauutu tauuauuauu uuaaygauat gggutuuatt 60uyggaguaua aguuuttuua ggguatggau uuuatuyggg tuaauuyguu uuutattauu 120uututggaga uuatuaaggu attuaaagau aaguagatuu auuygggutt tgguaguutg 180uuuuaguygu yygutuauuu tuaaguuuat uygguuuygu aagtauuuua auygguutag 240uaagauauyg utuuaygaay gguuuuaygy gtguuygguy gagggutgyg auyguygttt 300u 301529300DNAArtificial SequenceSynthetic polynucleotide 529tguuuaggut ggagtguagt gguaaaatut tggutuautt uaauutuygu utuuygggtt 60uaaguaattu tuutguutua guututuaag tagutgggat tauagguatg uauuatuaua 120uuuagutgat tttgtatttt tagtagagay ggggtttuau uaygttgttu aagutggtut 180uaaautuutg auutuaggtg atuuauuygu uttgguutuu uaaagtguyg ggattatagg 240tgtgaguuau yguauutggg uaattagtat tgtatttaag agtttatatt uatatuuata 300530300DNAArtificial SequenceSynthetic polynucleotide 530tatggatatg aatataaaut uttaaataua atautaattg uuuaggtgyg gtggutuaua 60uutataatuu ygguautttg ggagguuaag gygggtggat uauutgaggt uaggagtttg 120agauuagutt gaauaaygtg gtgaaauuuy gtututauta aaaatauaaa atuagutggg 180tgtgatggtg uatguutgta atuuuaguta uttgagaggu tgagguagga gaattguttg 240aauuygggag gyggaggttg aagtgaguua agattttguu autguautuu aguutgggua 300531300DNAArtificial SequenceSynthetic polynucleotide 531tgttauttua ttgaattutu ataatagutt aatgutatyg gttttuttut taattttggg 60gguatagtgg ggagataagu aaautgatau uuyggaggtt gagtgautua ttuatggaat 120guaguagguu ygtgagtuaa agygagtaua tgguaagauy gagtgaagut ggggaauaat 180aguuaaguua agagygtttt aaagatautt aguatuttua tuauautgaa tuutaaggtg 240auaguauttu uautygauag uaaaatgtua gattuaautg tttutttuyg gtuttuaaau 300532300DNAArtificial SequenceSynthetic polynucleotide 532gtttgaagau yggaaagaaa uagttgaatu tgauattttg utgtygagtg gaagtgutgt 60uauuttagga ttuagtgtga tgaagatgut aagtatuttt aaaaygutut tgguttggut 120attgttuuuu aguttuauty ggtuttguua tgtautygut ttgautuayg gguutgutgu 180attuuatgaa tgagtuautu aauutuyggg gtatuagttt guttatutuu uuautatguu 240uuuaaaatta agaagaaaau ygataguatt aagutattat gagaattuaa tgaagtaaua 300533300DNAArtificial SequenceSynthetic polynucleotide 533ttagtattau uaaatatyga gtuaaggguu tgatuaguuu uaaaagaatg agguautttt 60aatgtgauau uattuutggu agtutuaggt tyggututuu uagguuuygg atguagatgg 120utgttagggg utgguuatuu tuatutuaay ggtuutggaa gguauuautt tuaggguata 180tguuatgaut aauattuygg tgaguaatgu tgautuaaty gtagautgtt atttuatgtt 240uuuagtauuu tgtguaggaa gggaagggaa atgagtaata gatgtatuag tuuuattuaa 300534300DNAArtificial SequenceSynthetic polynucleotide 534ttgaatggga utgatauatu tattautuat ttuuuttuuu ttuutguaua gggtautggg 60aauatgaaat aauagtutay gattgagtua guattgutua uyggaatgtt agtuatggua 120tatguuutga aagtggtguu ttuuaggauy gttgagatga ggatgguuag uuuutaauag 180uuatutguat uygggguutg ggagaguyga auutgagaut guuaggaatg gtgtuauatt 240aaaagtguut uattuttttg gggutgatua gguuuttgau tygatatttg gtaatautaa 300535300DNAArtificial SequenceSynthetic polynucleotide 535agtggtggut gutgtttuty ggtgguagag atgatguutg gtttattutt agtaaagtgu 60ttaggaygut gaguutgagg ggututggaa tggaaaaaua aaauaaaaua aaauaaauyg 120gagguuygut utguutggut uutagagaua yguaaagutg gguaaaggaa ggagattgag 180gtgggautga gauattgttg uattgtgaat guuuyggttu uuuauutuut guuuuuygaa 240tuatgattgt tttatgyggt tatttttuuu tttggtgagg aaaatgggat gtggtgtuaa 300536300DNAArtificial SequenceSynthetic polynucleotide 536ttgauauuau atuuuatttt uutuauuaaa gggaaaaata auyguataaa auaatuatga 60ttyggggggu aggaggtggg gaauyggggu attuauaatg uaauaatgtu tuagtuuuau 120utuaatutuu ttuutttguu uagutttgyg tgtututagg aguuagguag agyggguutu 180yggtttgttt tgttttgttt tgtttttuua ttuuagaguu uutuaggutu agygtuutaa 240guautttaut aagaataaau uagguatuat ututguuauy gagaaauagu aguuauuaut 300537300DNAArtificial SequenceSynthetic polynucleotide 537ggggtyggua tgggutggag utuagagayg guuagutagg auttuaggau auauaguaaa 60utagutgygu uuygutgagg gtuagyguau aguyguuuau auaaggtgtu ututuuuygg 120gutututggg uyguygguut uutguttuuy gtguyguaga uygggattag autgtggayg 180yggggaagga agggggygtt gygaygggat uttgagggga guaggauttg uuuutguuuu 240tgyggygaag ututagguuu tgguaaggtt yggtauauyg gggguygutu utuuuuaggg 300538300DNAArtificial SequenceSynthetic polynucleotide 538uuutggggag gagygguuuu yggtgtauyg aauuttguua ggguutagag uttyguygua 60gggguagggg uaagtuutgu tuuuutuaag atuuygtygu aayguuuuut tuuttuuuyg 120ygtuuauagt utaatuuygg tutgygguay gggaaguagg agguyggygg uuuagagagu 180uyggggagag gauauuttgt gtgggyggut gtgygutgau uutuagyggg gyguagutag 240tttgutgtgt gtuutgaagt uutagutggu ygtututgag utuuaguuua tguygauuuu 300539300DNAArtificial SequenceSynthetic polynucleotide 539gtguayguag ggaaatauut uauagggtaa atttggatuy gattgagaau aggaaguuau 60agguuaatau aaggaggutu tgtgagaaua gatgauaaau uauaaguygg ggagggggag 120gaaagagutt tutggguutg ggggatgggy gaguuyguua guauauuaua uauagutgyg 180uttgguutua gtaatuaaaa uuatuattau agauutgayg gtttggutgu agutgtaaag 240agataaguat gttggaagag aaaauagggu uuyggtgauu ygguuttagg gtutgagygu 300540300DNAArtificial SequenceSynthetic polynucleotide 540ygutuagauu utaagguygg gtuauygggg uuutgttttu tuttuuaaua tguttatutu 60tttauagutg uaguuaaauy gtuaggtutg taatgatggt tttgattaut gagguuaagy 120guagutgtgt gtggtgtgut ggygggutyg uuuatuuuuu agguuuagaa agututttuu 180tuuuuutuuu ygguttgtgg tttgtuatut gttutuauag aguutuuttg tattgguutg 240tgguttuutg ttutuaatyg gatuuaaatt tauuutgtga ggtatttuuu tgygtguaua 300541300DNAArtificial SequenceSynthetic polynucleotide 541tgtgygggua gtgggttgtg yggguagtgg gttgtguatu yggatgtgta guautuauau 60auttygggtg aututtuutg ggtaagutgt ggatgtgagt ggggguagua tutguygtga 120utuattutut uututttuua ttuuaaguyg ggtgggggag tttgggattt uuagauaagg 180uutggutuuu uutgguauag agggtgggag tggggatggg gagggaggag ggaagggtua 240tgggaaggtg ggguuatgtt ttgtgutuaa tgaautgaga agggggaggg ttuuagutgg 300542300DNAArtificial SequenceSynthetic polynucleotide 542uagutggaau uutuuuuutt utuagttuat tgaguauaaa auatgguuuu auuttuuuat 60gauuuttuuu tuutuuutuu uuatuuuuau tuuuauuutu tgtguuaggg ggaguuaggu 120uttgtutgga aatuuuaaau tuuuuuauuy gguttggaat ggaaagagga gagaatgagt 180uaygguagat gutguuuuua utuauatuua uaguttauuu aggaagagtu auuygaagtg 240tgtgagtgut

auauatuygg atguauaauu uautguuygu auaauuuaut guuyguauaa 300543300DNAArtificial SequenceSynthetic polynucleotide 543guaautggyg utgggtaggu aaaguyggga gaaautgutg agaygaggtt aggatttaau 60utttaaattu tggaguuaty ggaaauygag gggaggayga ygggtgtygg tgutaatgag 120gutgggggyg ggygatgygy ggtggguutu ygagtuyggg guaggtutyg ggggttuuuy 180ggggaagguu utgggaguuu ttgguuutgg ygguutuygu uatuagautg ggaatgtutu 240tgattgggtg guuaggaggy ggtgguuutu utuuuyguuu agutgagggg tgtygtuttu 300544300DNAArtificial SequenceSynthetic polynucleotide 544gaagaygaua uuuutuagut gggyggggag gaggguuauy guutuutggu uauuuaatua 60gagauattuu uagtutgatg gyggagguyg uuaggguuaa gggutuuuag gguuttuuuy 120ggggaauuuu ygagauutgu uuyggautyg gagguuuauy gyguatyguu yguuuuuagu 180utuattagua uygauauuyg tygtuutuuu utyggtttuy gatggutuua gaatttaaag 240gttaaatuut aauutygtut uaguagtttu tuuygguttt guutauuuag yguuagttgu 300545300DNAArtificial SequenceSynthetic polynucleotide 545ggguauuutu tggtguttuu agguutgtga attgguauag uaggauuaua gauutuuaag 60gtguuuauut gggggutuag aauuutggyg gggaaggtua gtgutatuuu auyggagaag 120agauutagtu tagutgaguu uutgguuagy gguaaggagg aaaggatgaa uatuaguuay 180guutgguaut gautguuaua guuagaguut yguuuaguuu aagaatgttt utgttutaag 240auttttttut tttttgtatt ttagaaatta tuauagguaa atgtuauutt gaagauuygg 300546300DNAArtificial SequenceSynthetic polynucleotide 546uygggtuttu aaggtgauat ttguutgtga taatttutaa aatauaaaaa agaaaaaagt 60uttagaauag aaauattutt gggutgggyg aggututggu tgtgguagtu agtguuaggy 120gtggutgatg ttuatuuttt uutuuttguy gutgguuagg ggutuaguta gautaggtut 180uttutuyggt gggataguau tgauuttuuu yguuagggtt utgaguuuuu aggtggguau 240uttggaggtu tgtggtuutg utgtguuaat tuauagguut ggaaguauua gagggtguuu 300547300DNAArtificial SequenceSynthetic polynucleotide 547utuatggaga ggaguagaga tguaggaaay guaauaguag uaygguagaa ayguaggaga 60aauaguuuyg uutuagaguy guuuauutuu tuuyguuatg uuaggaaggg uuagtgtuuu 120tuuagayguy ggtgautgtu aygtuagaua ygtgaygtgt ggutgtguuu agattuttgg 180yggtgaguuu yggygaggga uuuagyggtu tuuyggygtu tggtttaggg ggggatutuy 240guaagauuuy guuyguaygt ggutuutgtg agggguautg ygygygaagg utgtggtutg 300548300DNAArtificial SequenceSynthetic polynucleotide 548uagauuauag uuttygygyg uagtguuuut uauaggaguu aygtgygggy ggggtuttgy 60ggagatuuuu uuutaaauua gayguyggga gauygutggg tuuutyguyg gggutuauyg 120uuaagaatut ggguauaguu auaygtuayg tgtutgaygt gauagtuauy ggygtutgga 180gggauautgg uuuttuutgg uatggyggga ggaggtgggy ggututgagg yggggutgtt 240tutuutgygt ttutguygtg utgutgttgy gtttuutgua tututgutuu tutuuatgag 300549300DNAArtificial SequenceSynthetic polynucleotide 549ututuuautg tguagguuau utgtagggau agtguuagtg ggtgtaggag aggtggygag 60gutguaguag tgygggatgg gutuuuuaua uuuuuaaata utuuauatgg ggtuyggggu 120uttuuuagga uutggguuag gtgyguaygu utgggygggg uuaguuagut ygtgutgagt 180uauygggtgu ygtuagtgag gguutgguuu uauuutyggg aauuauyggt gutggttttu 240uuayggutgu tguuygutgt ggguuttgut gtuauuuaua agguuutggg agguuutguu 300550300DNAArtificial SequenceSynthetic polynucleotide 550gguaggguut uuuaggguut tgtgggtgau aguaagguuu auagygggua guaguygtgg 60gaaaauuagu auyggtggtt uuygagggtg ggguuagguu utuautgayg guauuyggtg 120autuaguayg agutggutgg uuuyguuuag gygtgyguau utgguuuagg tuutgggaag 180guuuyggauu uuatgtggag tatttggggg tgtggggagu uuatuuygua utgutguagu 240utyguuauut utuutauauu uautgguaut gtuuutauag gtgguutgua uagtggagag 30055119DNAArtificial SequenceSynthetic polynucleotide 551gggagaagag attggaaaa 1955227DNAArtificial SequenceSynthetic polynucleotide 552ctaaaaacct aacactaaca acataat 2755320DNAArtificial SequenceSynthetic polynucleotide 553tgttgtttaa aatgttgttt 2055420DNAArtificial SequenceSynthetic polynucleotide 554aaccctaaat aattcttctc 2055518DNAArtificial SequenceSynthetic polynucleotide 555gggttgggtt gaggtttt 1855625DNAArtificial SequenceSynthetic polynucleotide 556acaccttaca tctcatttac aactc 2555721DNAArtificial SequenceSynthetic polynucleotide 557aatttgtgaa aagtttgtgt a 2155818DNAArtificial SequenceSynthetic polynucleotide 558cccaatcacc tttaatct 1855920DNAArtificial SequenceSynthetic polynucleotide 559gttgggattt gaaatagtga 2056020DNAArtificial SequenceSynthetic polynucleotide 560cctccactca cctaaaactt 2056120DNAArtificial SequenceSynthetic polynucleotide 561ttggttagtg attatttatt 2056222DNAArtificial SequenceSynthetic polynucleotide 562aaaaattaat ataaaattaa aa 2256319DNAArtificial SequenceSynthetic polynucleotide 563tttgtaggga gttagggat 1956420DNAArtificial SequenceSynthetic polynucleotide 564tcctctatct caccctaaat 2056523DNAArtificial SequenceSynthetic polynucleotide 565tttgattgaa ttatttgtgt att 2356621DNAArtificial SequenceSynthetic polynucleotide 566actcccttac tcctaaacac t 2156719DNAArtificial SequenceSynthetic polynucleotide 567agtggagatg gtagggaga 1956823DNAArtificial SequenceSynthetic polynucleotide 568cccaaaacta aaaccaaata taa 2356918DNAArtificial SequenceSynthetic polynucleotide 569ttgtggttaa atttattg 1857018DNAArtificial SequenceSynthetic polynucleotide 570acccaacaaa ataatatc 1857122DNAArtificial SequenceSynthetic polynucleotide 571tgaggtagag ttgtgtgtat at 2257221DNAArtificial SequenceSynthetic polynucleotide 572atcaatcaat tctcattaaa c 2157319DNAArtificial SequenceSynthetic polynucleotide 573ggaagttagg aagggttgt 1957421DNAArtificial SequenceSynthetic polynucleotide 574ctccaactcc aactaaaact c 2157519DNAArtificial SequenceSynthetic polynucleotide 575ttgggtattg atttatttt 1957623DNAArtificial SequenceSynthetic polynucleotide 576aaattctacc tacaaactat aca 2357725DNAArtificial SequenceSynthetic polynucleotide 577aggatgaagt aataattaaa tattg 2557819DNAArtificial SequenceSynthetic polynucleotide 578cccactctac caactaaac 1957920DNAArtificial SequenceSynthetic polynucleotide 579aggtttgtgt tagtataaat 2058024DNAArtificial SequenceSynthetic polynucleotide 580ttcttaccta tataattaat aata 2458119DNAArtificial SequenceSynthetic polynucleotide 581gttgggtgaa ttttattag 1958220DNAArtificial SequenceSynthetic polynucleotide 582tcaaaaccta aactctaaca 2058324DNAArtificial SequenceSynthetic polynucleotide 583ggattggttt tatatagaaa gtat 2458426DNAArtificial SequenceSynthetic polynucleotide 584caaataataa atcataactc ttaact 2658518DNAArtificial SequenceSynthetic polynucleotide 585tggggtagtt gatggttt 1858626DNAArtificial SequenceSynthetic polynucleotide 586ctttctaaca aaataaaaaa atttaa 2658728DNAArtificial SequenceSynthetic polynucleotide 587ttgtatttga agtttgtaga gatttata 2858819DNAArtificial SequenceSynthetic polynucleotide 588tttcctccaa caactcaat 1958927DNAArtificial SequenceSynthetic polynucleotide 589ttatgagtat gtagtagggt tattata 2759022DNAArtificial SequenceSynthetic polynucleotide 590aaaatatcaa acaaatttat cc 2259123DNAArtificial SequenceSynthetic polynucleotide 591tggttgtttg ttttttatgt att 2359218DNAArtificial SequenceSynthetic polynucleotide 592tccctacctc ccaaattc 1859323DNAArtificial SequenceSynthetic polynucleotide 593tatgatgatt gttgtagtgt aga 2359422DNAArtificial SequenceSynthetic polynucleotide 594cctccctaat aactaaaaat ac 2259520DNAArtificial SequenceSynthetic polynucleotide 595ggtggttttg atatttagtg 2059620DNAArtificial SequenceSynthetic polynucleotide 596cccaattacc taacaaatta 2059719DNAArtificial SequenceSynthetic polynucleotide 597tgggataggt gtagatatg 1959823DNAArtificial SequenceSynthetic polynucleotide 598caacaaaaac taaaacacta tac 2359918DNAArtificial SequenceSynthetic polynucleotide 599tttgggattg gttatttt 1860020DNAArtificial SequenceSynthetic polynucleotide 600aaacccctta actctatacc 2060122DNAArtificial SequenceSynthetic polynucleotide 601gatttttttg agaagagtat ag 2260221DNAArtificial SequenceSynthetic polynucleotide 602aaccactacc acctaaatat a 2160318DNAArtificial SequenceSynthetic polynucleotide 603ggaggatagg gtgtgatt 1860427DNAArtificial SequenceSynthetic polynucleotide 604acatttttaa ctctaactaa aaataaa 2760518DNAArtificial SequenceSynthetic polynucleotide 605tggaaatgag gtgagttt 1860626DNAArtificial SequenceSynthetic polynucleotide 606aaaaaaaaat aaaataacaa taacta 2660719DNAArtificial SequenceSynthetic polynucleotide 607tggagagttt agtttgttt 1960819DNAArtificial SequenceSynthetic polynucleotide 608caaaaaaaaa tctaacaac 1960920DNAArtificial SequenceSynthetic polynucleotide 609tgggttttag ttatgtggtt 2061026DNAArtificial SequenceSynthetic polynucleotide 610atcaataata tccaacaaaa taatat 2661127DNAArtificial SequenceSynthetic polynucleotide 611tttttttagt ttttgtatat atattag 2761219DNAArtificial SequenceSynthetic polynucleotide 612acccaaataa tcaactctt 1961318DNAArtificial SequenceSynthetic polynucleotide 613gtggtttttg gagattta 1861425DNAArtificial SequenceSynthetic polynucleotide 614aaacaaacta caaataaaat aatac 2561519DNAArtificial SequenceSynthetic polynucleotide 615gggttatagg tttgagtta 1961620DNAArtificial SequenceSynthetic polynucleotide 616ccattaaaaa aaataaaatc 2061723DNAArtificial SequenceSynthetic polynucleotide 617ttggtagatt tagtaaattt att 2361822DNAArtificial SequenceSynthetic polynucleotide 618aaacttaaac aaccctatat ac 2261927DNAArtificial SequenceSynthetic polynucleotide 619atggttttaa agagtagtag tatagtt 2762020DNAArtificial SequenceSynthetic polynucleotide 620aaatttactc atcccacttc 2062118DNAArtificial SequenceSynthetic polynucleotide 621aggggttggg atattgtt 1862225DNAArtificial SequenceSynthetic polynucleotide 622aaaaatttct cctacaaaaa actaa 2562320DNAArtificial SequenceSynthetic polynucleotide 623atgggtgttt ggaattttta 2062425DNAArtificial SequenceSynthetic polynucleotide 624ctacctcaac ctcctaaata actaa 2562522DNAArtificial SequenceSynthetic polynucleotide 625gtgttttgtg gtaaagatat ag 2262624DNAArtificial SequenceSynthetic polynucleotide 626attcttaaat taattcaact acat 2462720DNAArtificial SequenceSynthetic polynucleotide 627tgggggtaaa agttatagtt 2062821DNAArtificial SequenceSynthetic polynucleotide 628aaaaaacaaa aaaccaaata c 2162919DNAArtificial SequenceSynthetic polynucleotide 629gttttttggt tagtgtgtt 1963022DNAArtificial SequenceSynthetic polynucleotide 630ccccatactt ctatactata at 2263123DNAArtificial SequenceSynthetic polynucleotide 631ttgttgtttt taaagaaatt ata 2363224DNAArtificial SequenceSynthetic polynucleotide 632atcatctaaa cttaactcat ctaa 2463320DNAArtificial SequenceSynthetic polynucleotide 633atttttgggt gttttatatt 2063418DNAArtificial SequenceSynthetic polynucleotide 634aaacctcaaa caataaca 1863524DNAArtificial SequenceSynthetic polynucleotide 635attaaggata tttaggagag taag 2463620DNAArtificial SequenceSynthetic polynucleotide 636acaccacaac ttcaaactac 2063723DNAArtificial SequenceSynthetic polynucleotide 637tgaggaagag agaagagatg ata 2363830DNAArtificial SequenceSynthetic polynucleotide 638aaaactaaac tataaaacaa aacaaaacta 3063920DNAArtificial SequenceSynthetic polynucleotide 639ggtggaggtg ttttttatag 2064023DNAArtificial SequenceSynthetic polynucleotide 640ccaaatacta ctttcaaaat aca 2364121DNAArtificial SequenceSynthetic polynucleotide 641atggattatt attgtgttat t 2164219DNAArtificial SequenceSynthetic polynucleotide 642catctcaacc tcatactaa 1964322DNAArtificial SequenceSynthetic polynucleotide 643ggatgattta gtagggattg ag 2264423DNAArtificial SequenceSynthetic polynucleotide 644ccaaataaaa accattctct aac 2364524DNAArtificial SequenceSynthetic polynucleotide 645ttggattaag tatttttgat atta 2464623DNAArtificial SequenceSynthetic polynucleotide 646tccctaaacc atatattact aaa 2364722DNAArtificial SequenceSynthetic polynucleotide 647gggtagtttg gtgattatta tt 2264819DNAArtificial SequenceSynthetic polynucleotide 648cccttcccta ctcacaata 1964923DNAArtificial SequenceSynthetic polynucleotide 649atttggttag tgatttagtt att 2365021DNAArtificial SequenceSynthetic polynucleotide 650tcccacttaa aaaattctat a 2165121DNAArtificial SequenceSynthetic polynucleotide 651agtggggaag gtaattgtta t

2165230DNAArtificial SequenceSynthetic polynucleotide 652ctttctaata aaaatttact aaaacctcta 3065324DNAArtificial SequenceSynthetic polynucleotide 653tttggttagt tttatttttg attg 2465420DNAArtificial SequenceSynthetic polynucleotide 654attcctccct atccctattc 2065519DNAArtificial SequenceSynthetic polynucleotide 655gggatagggg ttagagtaa 1965620DNAArtificial SequenceSynthetic polynucleotide 656tccataaaaa caaaacactc 2065725DNAArtificial SequenceSynthetic polynucleotide 657ttttttagta tgagttataa attat 2565823DNAArtificial SequenceSynthetic polynucleotide 658aaaacaaaat ctacctatat att 2365923DNAArtificial SequenceSynthetic polynucleotide 659ttttattaat aaagtaggta tga 2366020DNAArtificial SequenceSynthetic polynucleotide 660acctttctca aaattactaa 2066122DNAArtificial SequenceSynthetic polynucleotide 661atagggttga ggttagagtt at 2266218DNAArtificial SequenceSynthetic polynucleotide 662cctcctctcc acaataaa 1866326DNAArtificial SequenceSynthetic polynucleotide 663tttaagtttt tttttagttt tgtagt 2666418DNAArtificial SequenceSynthetic polynucleotide 664ccccatcctc tctatctc 1866526DNAArtificial SequenceSynthetic polynucleotide 665aaatttaaaa tttagaggtt tttata 2666624DNAArtificial SequenceSynthetic polynucleotide 666aaacttcaca cacaaatcta tatt 2466725DNAArtificial SequenceSynthetic polynucleotide 667tttttatttt attttttatt tttaa 2566824DNAArtificial SequenceSynthetic polynucleotide 668atacctccct aattatatta ttaa 2466925DNAArtificial SequenceSynthetic polynucleotide 669ttttagaata tttaaagaag ttagt 2567019DNAArtificial SequenceSynthetic polynucleotide 670taacctcact ttcctatca 1967126DNAArtificial SequenceSynthetic polynucleotide 671aatttagtat aagatttgat ttgtta 2667220DNAArtificial SequenceSynthetic polynucleotide 672ccacctactc cttcctatac 2067321DNAArtificial SequenceSynthetic polynucleotide 673ttttttgaaa ttgtatgtta t 2167421DNAArtificial SequenceSynthetic polynucleotide 674caaatcctta aaattctata a 2167518DNAArtificial SequenceSynthetic polynucleotide 675tttgaagtgg tgttttag 1867618DNAArtificial SequenceSynthetic polynucleotide 676ccaaaattct tccatact 1867720DNAArtificial SequenceSynthetic polynucleotide 677tgggtattta gttttttgtg 2067823DNAArtificial SequenceSynthetic polynucleotide 678aacaactacc tccttttact aat 2367919DNAArtificial SequenceSynthetic polynucleotide 679tatggtagga ggtggagtt 1968019DNAArtificial SequenceSynthetic polynucleotide 680cccaatttta aaacaatac 1968122DNAArtificial SequenceSynthetic polynucleotide 681agaggaagta aggttattag tt 2268220DNAArtificial SequenceSynthetic polynucleotide 682accaaacaaa caatatctaa 2068324DNAArtificial SequenceSynthetic polynucleotide 683ggttttaatt atgatttaat taga 2468422DNAArtificial SequenceSynthetic polynucleotide 684cctacactca aatttacctc ta 2268523DNAArtificial SequenceSynthetic polynucleotide 685aatgggtagt tgatataatt att 2368621DNAArtificial SequenceSynthetic polynucleotide 686cacaaaatcc taaaactaaa a 2168722DNAArtificial SequenceSynthetic polynucleotide 687aggattagtg gaaatgaaaa ta 2268823DNAArtificial SequenceSynthetic polynucleotide 688taacctcaaa acaacttcta aac 2368925DNAArtificial SequenceSynthetic polynucleotide 689ttttttttat agagaagtat tttag 2569018DNAArtificial SequenceSynthetic polynucleotide 690cccattacaa aactatcc 1869119DNAArtificial SequenceSynthetic polynucleotide 691ggtgagtttg tggttagtg 1969222DNAArtificial SequenceSynthetic polynucleotide 692ttttctaaaa aaatccaatc ta 2269319DNAArtificial SequenceSynthetic polynucleotide 693aatggatagg ttggaatag 1969423DNAArtificial SequenceSynthetic polynucleotide 694aaaaaaaaaa aaaaactaat tac 2369522DNAArtificial SequenceSynthetic polynucleotide 695gagttattta gtttggttag gt 2269624DNAArtificial SequenceSynthetic polynucleotide 696actcaactta aaaaatcact atac 2469722DNAArtificial SequenceSynthetic polynucleotide 697ttttttttgg ttttttggtt tt 2269818DNAArtificial SequenceSynthetic polynucleotide 698tcccccacac ccatataa 1869925DNAArtificial SequenceSynthetic polynucleotide 699ttaaaaaaaa gtataatgag tagga 2570019DNAArtificial SequenceSynthetic polynucleotide 700cccacaaaaa ctctctaca 1970124DNAArtificial SequenceSynthetic polynucleotide 701aaaggaggtt gagttagaaa gtag 2470226DNAArtificial SequenceSynthetic polynucleotide 702aactatttaa cttacttaac cacacc 2670325DNAArtificial SequenceSynthetic polynucleotide 703ggtgtggtta agtaagttaa atagt 2570418DNAArtificial SequenceSynthetic polynucleotide 704taccccttcc tcttcaac 1870524DNAArtificial SequenceSynthetic polynucleotide 705ttttgatatg atttatgatt atat 2470620DNAArtificial SequenceSynthetic polynucleotide 706ttttccacta aacaacacta 2070719DNAArtificial SequenceSynthetic polynucleotide 707tttgagggtt gttttagat 1970826DNAArtificial SequenceSynthetic polynucleotide 708actcacaaaa aataactaat aactat 2670921DNAArtificial SequenceSynthetic polynucleotide 709aaaggaggta ggggagatat a 2171023DNAArtificial SequenceSynthetic polynucleotide 710tcaaaataaa aaccaaaatt ctc 2371122DNAArtificial SequenceSynthetic polynucleotide 711aggttaagtt ggtagaggta ga 2271225DNAArtificial SequenceSynthetic polynucleotide 712caaactctaa actcaaaata tattc 2571324DNAArtificial SequenceSynthetic polynucleotide 713tttttatttt agttttttga gtag 2471420DNAArtificial SequenceSynthetic polynucleotide 714ccctacaaca ctcctatcta 2071519DNAArtificial SequenceSynthetic polynucleotide 715tttggagtta ggttgatag 1971621DNAArtificial SequenceSynthetic polynucleotide 716caacaatact ctcacttaca c 2171725DNAArtificial SequenceSynthetic polynucleotide 717agaaagattt ttaaatattt ttaat 2571821DNAArtificial SequenceSynthetic polynucleotide 718aaacctctaa tacacaacaa a 2171923DNAArtificial SequenceSynthetic polynucleotide 719ttttgagttt tttttttaag tat 2372022DNAArtificial SequenceSynthetic polynucleotide 720caaacaaaac aacacttaat ac 2272119DNAArtificial SequenceSynthetic polynucleotide 721ggttgaggtg ggtggatta 1972230DNAArtificial SequenceSynthetic polynucleotide 722tttttttttt ttttttttaa aataaaatct 3072320DNAArtificial SequenceSynthetic polynucleotide 723gggtgtttgt aattttagtt 2072423DNAArtificial SequenceSynthetic polynucleotide 724acctttaaca acctaacaat ata 2372521DNAArtificial SequenceSynthetic polynucleotide 725gggtagatga tatggtagtg a 2172628DNAArtificial SequenceSynthetic polynucleotide 726aaaaaataaa aaataactaa aacaatat 2872722DNAArtificial SequenceSynthetic polynucleotide 727aggaagtgtt taagaagtag aa 2272823DNAArtificial SequenceSynthetic polynucleotide 728cctaaaactc taaatacaat ctc 2372921DNAArtificial SequenceSynthetic polynucleotide 729tttttaattt ttgtttgtat t 2173020DNAArtificial SequenceSynthetic polynucleotide 730aaaccacaat ctatttctaa 2073123DNAArtificial SequenceSynthetic polynucleotide 731ttagaaaaga ataattatag ttg 2373219DNAArtificial SequenceSynthetic polynucleotide 732accctaaaaa aataaaatc 1973326DNAArtificial SequenceSynthetic polynucleotide 733ttgtattagt aaataaagtg tatttt 2673420DNAArtificial SequenceSynthetic polynucleotide 734aaccctttct acaaatctac 2073518DNAArtificial SequenceSynthetic polynucleotide 735aggggtgggt ggaagaat 1873631DNAArtificial SequenceSynthetic polynucleotide 736ctcctcaata aaataaaaat cctaaaaaat a 3173720DNAArtificial SequenceSynthetic polynucleotide 737gggttaatta gttgttttat 2073821DNAArtificial SequenceSynthetic polynucleotide 738cctacaaata tatcacacac t 2173921DNAArtificial SequenceSynthetic polynucleotide 739tttgttaaat aggtggttag a 2174020DNAArtificial SequenceSynthetic polynucleotide 740acctcaacct cctaaataac 2074122DNAArtificial SequenceSynthetic polynucleotide 741tagggtttag agtaggaggt ag 2274224DNAArtificial SequenceSynthetic polynucleotide 742caaaaaatat aaatcaaaaa catc 2474321DNAArtificial SequenceSynthetic polynucleotide 743gggattatag gtatttatta t 2174422DNAArtificial SequenceSynthetic polynucleotide 744taaaaattaa aaatcatact ta 2274520DNAArtificial SequenceSynthetic polynucleotide 745aagtgatttt tagggagtgt 2074623DNAArtificial SequenceSynthetic polynucleotide 746tccataataa cctcatttta ata 2374719DNAArtificial SequenceSynthetic polynucleotide 747tttttggttg aggtttagt 1974821DNAArtificial SequenceSynthetic polynucleotide 748aaacaacaca actcttatca c 2174924DNAArtificial SequenceSynthetic polynucleotide 749tatggtgatt aaagtataat agtt 2475021DNAArtificial SequenceSynthetic polynucleotide 750tcctaaataa aaaacaacat a 2175123DNAArtificial SequenceSynthetic polynucleotide 751tgaaaatgtt tttagttttt att 2375222DNAArtificial SequenceSynthetic polynucleotide 752aaatacccta cctcttatct aa 2275320DNAArtificial SequenceSynthetic polynucleotide 753gatggttaat ttttttattt 2075419DNAArtificial SequenceSynthetic polynucleotide 754actccttcaa caaactaac 1975518DNAArtificial SequenceSynthetic polynucleotide 755aggggatatt tttaggtt 1875623DNAArtificial SequenceSynthetic polynucleotide 756ccaatctatt cctatataat taa 2375720DNAArtificial SequenceSynthetic polynucleotide 757aggagagttt ggaaatatag 2075822DNAArtificial SequenceSynthetic polynucleotide 758caattctaaa ttaaacctta tt 2275923DNAArtificial SequenceSynthetic polynucleotide 759aataatggta gtagttttat tag 2376021DNAArtificial SequenceSynthetic polynucleotide 760ttcctatatt aacaacttac a 2176119DNAArtificial SequenceSynthetic polynucleotide 761ttttttggta gatttttat 1976225DNAArtificial SequenceSynthetic polynucleotide 762aaattaattt ctattattta tatta 2576318DNAArtificial SequenceSynthetic polynucleotide 763aggtggttgg ggagagtg 1876428DNAArtificial SequenceSynthetic polynucleotide 764ccctaaaata aatcaaaaaa aaccttaa 2876519DNAArtificial SequenceSynthetic polynucleotide 765aggtttaggt ggggtgaat 1976624DNAArtificial SequenceSynthetic polynucleotide 766taaaatcatc aaaatccctt aaaa 2476725DNAArtificial SequenceSynthetic polynucleotide 767ttttttttta ggttatagga gtatt 2576818DNAArtificial SequenceSynthetic polynucleotide 768atccccacaa aacacata 1876922DNAArtificial SequenceSynthetic polynucleotide 769tagggtaaat attgggatta tt 2277020DNAArtificial SequenceSynthetic polynucleotide 770tttccacctc aaaacttaac 2077121DNAArtificial SequenceSynthetic polynucleotide 771gggtgtttgt atttttatat t 2177218DNAArtificial SequenceSynthetic polynucleotide 772acctcccaaa accataac 1877320DNAArtificial SequenceSynthetic polynucleotide 773gatgtgagtg gtgaggtggt 2077422DNAArtificial SequenceSynthetic polynucleotide 774caaacccttc caaaacataa ac 2277520DNAArtificial SequenceSynthetic polynucleotide 775tgggattata ggtatgtatt 2077625DNAArtificial SequenceSynthetic polynucleotide 776caatttcatt tataaatata aatat 2577722DNAArtificial SequenceSynthetic polynucleotide 777aggggttggt

tatttttatt tt 2277829DNAArtificial SequenceSynthetic polynucleotide 778tttttaatat ttaattttta ccttcaact 2977920DNAArtificial SequenceSynthetic polynucleotide 779ggtaagttgt ggatgtgagt 2078022DNAArtificial SequenceSynthetic polynucleotide 780aaaaaaaacc aaaccttatc ta 2278119DNAArtificial SequenceSynthetic polynucleotide 781tttttaggat ttgggttag 1978223DNAArtificial SequenceSynthetic polynucleotide 782aaccttataa ataacaacaa aac 23

Claims

1. A method of detecting methylation or unmethylation of a thyroid nodule DNA molecule of a subject, the method comprising: (i) isolating a thyroid nodule DNA molecule from a thyroid nodule of said subject thereby forming an isolated thyroid nodule DNA molecule, (ii) contacting said isolated thyroid nodule DNA molecule with a bisulfite salt thereby forming a reacted thyroid nodule DNA molecule, (iii) detecting the presence or absence of uracil in said reacted thyroid nodule DNA molecule at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of said thyroid nodule DNA molecule of said subject.

2. (canceled)

3. The method of claim 1, the method further comprising: (i) isolating a plurality of thyroid nodule DNA molecules from said thyroid nodule of said subject thereby forming a plurality of isolated thyroid nodule DNA molecules, wherein said isolated thyroid nodule DNA molecule forms part of said plurality of isolated thyroid nodule DNA molecules, (ii) contacting said plurality of isolated thyroid nodule DNA molecules with said bisulfite salt thereby forming a plurality of reacted thyroid nodule DNA molecules, wherein said reacted thyroid nodule DNA molecule forms part of said plurality of reacted thyroid nodule DNA molecules, (iii) detecting the level of reacted thyroid nodule DNA molecules in said plurality of reacted thyroid nodule DNA molecules having a uracil at a methylation site set forth in Table 1, thereby detecting the level of methylation or unmethylation in said plurality of thyroid nodule DNA molecules of said subject.

4. The method of claim 3, further comprising determining the level of uracil in said reacted thyroid nodule DNA molecule at a plurality methylation sites set forth in Table 1, wherein said methylation site forms a part of said plurality of methylation sites.

5. The method of claim 4, wherein said uracil level is (a) above a threshold as set forth in Table 2; (b) above a threshold as set forth in Table 3; or (c) below a threshold as set forth in Table 4.

6.-8. (canceled)

9. The method of claim 1, wherein said thyroid nodule is a specimen obtained by biopsy or by surgical resection of said subject.

10. (canceled)

11. (canceled)

12. A method of detecting a thyroid cancer or risk of developing thyroid cancer in a subject in need thereof, said method comprising detecting methylation or unmethylation of a thyroid nodule DNA molecule of said subject by the method set forth in claim 1.

13. The method of claim 12, wherein said subject (a) is a woman; (b) is about 20 to about 55 years old; (c) has a mutated Ret Proto-Oncogene; (d) has a grandparent, parent, or sibling who has been diagnosed with thyroid cancer; (e) self-identifies as being Caucasian or Asian; and/or (f) has or has had breast cancer.

14.-21. (canceled)

22. The method of claim 12, wherein said subject has undergone thyroid surgery, radiation therapy, radioactive iodine therapy, chemotherapy, thyroid hormone therapy, and administration of an active agent, before said determination.

23. The method of claim 22, wherein said active agent is chosen from Cabozantinib-S-Malate, Caprelsa (Vandetanib), Cometriq (Cabozantinib-S-Malate), Doxorubicin Hydrochloride, Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate), Nexavar (Sorafenib Tosylate), and Sorafenib Tosylate.

24. A method of treating thyroid cancer in a subject determined by the method as set forth in claim 12, comprising administering to said subject an active agent for treating thyroid cancer.

25.-27. (canceled)

28. The method of claim 1, wherein said bisulfite salt is sodium bisulfite.

29. The method of claim 12, further comprising determining a papillary thyroid carcinoma (PTC) methylation alteration score for said subject, wherein the PTC methylation alteration score is equal to: the number of methylation sites in Table 1 having a uracil level equal to or greater than the corresponding threshold level set forth in Table 2.

30. The method of claim 12, further comprising determining a benign thyroid nodule (BTN) methylation alteration score for said subject, wherein the BTN methylation alteration score is equal to: (a) the number of methylation sites in Table 1 having a uracil level equal to or greater than the corresponding threshold level set forth in Table 3; (b) the number of methylation sites in Table 1 having a uracil level equal to or less than the corresponding threshold level set forth in Table 4; or (c) the number of methylation sites in Table 1 having a uracil level equal to or greater than the corresponding threshold level set forth in Table 3 plus the number of methylation sites in Table 1 having a uracil level equal to or less than the corresponding threshold level set forth in Table 4.

31. The method of claim 29, further comprising calculating a Composite Cancer Risk Score for said subject, wherein said Composite Cancer Risk Score for said subject equals: [the PTC methylation alteration score for said subject]/[BTN methylation alteration score for said subject]; or [(the PTC methylation alteration score for said subject)+1]/[(BTN methylation alteration score for said subject)+1].

32. (canceled)

33. (canceled)

34. The method of claim 29, wherein said subject is identified as being at risk of developing thyroid cancer or diagnosed as having thyroid cancer if (a) the PTC methylation alteration score for said subject is at least 5, 6, 7, 8, 9, or 10; (b) the BTN methylation alteration score for said subject is at least 5, 6, 7, 8, 9, or 10; and/or (c) the Composite Cancer Risk Score for said subject is at least about 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3.0.

35. The method of claim 29, wherein said subject is treated for thyroid cancer or directed to receive additional screening for thyroid cancer if (a) the PTC methylation alteration score for said subject is at least 5, 6, 7, 8, 9, or 10; (b) the BTN methylation alteration score for said subject is at least 5, 6, 7, 8, 9, or 10; and/or (c) the Composite Cancer Risk Score for said subject is at least about 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3.0.

36. A deoxyribonucleic acid at least 5 to 100 nucleotides in length comprising a uracil-containing sequence that is identical to a sequence of at least a 5 contiguous nucleotides within a sequence chosen from SEQ ID NO:1 to SEQ ID NO:550.

37. (canceled)

38. The deoxyribonucleic acid of claim 36, wherein said sequence comprises a methylation site set forth in Table 1.

39.-42. (canceled)

43. A kit comprising a plurality of nucleic acids each independently comprising SEQ ID NO:551 to SEQ ID NO:782, wherein each nucleic acid of said plurality is unique.

44. (canceled)

45. (canceled)

46. A system for detecting methylation or unmethylation of a thyroid nodule deoxyribonucleic acid (DNA) of a subject, the system comprising: at least one processor, and at least one memory including program code which when executed by the at least one memory provides operations comprising: isolating a thyroid nodule DNA molecule from a thyroid nodule of said subject thereby forming an isolated thyroid nodule DNA molecule; contacting said isolated thyroid nodule DNA molecule with a bisulfite salt thereby forming a reacted thyroid nodule DNA molecule; detecting the presence or absence of uracil in said reacted thyroid nodule DNA molecule at a methylation site set forth in Table 1, thereby detecting methylation or unmethylation of said thyroid nodule DNA molecule of said subject; generating a diagnosis for said subject based at least in part on the presence or absence of uracil in said reacted thyroid nodule DNA molecule at the methylation site set forth in Table 1; and providing, via a user interface, the diagnosis for said subject.

47.-58. (canceled)